Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.64089514
Co immunoprecipitation analysis showed a constitutive association between c Src and PI3K , which was enhanced by PTH treatment , suggesting that the cytosolic tyrosine kinase forms an immunocomplex with PI3K probably via the N SH 2 domain of the p85alpha regulatory subunit . 0.64089514^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
A common RXL motif was found in proline rich ligands that were selected from a biased combinatorial peptide library on the basis of their ability to bind specifically to the SH 3 domains from phosphatidylinositol 3 kinase ( PI3K ) or c Src . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Mitotic , tyrosine phosphorylated Sam 68 bound selectively to recombinant SH 2 domains with significantly different affinities ( c Src approximately Ras GTPase activating protein > p 85 alpha ( amino terminal ) > Grb 2 > > p 85 alpha ( COOH terminal ) ) . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The topology of secondary structural elements of the PI3K SH 3 domain is similar to those of the SH 3 domains from c Src and alpha spectrin , suggesting that the SH 3 family has a common tertiary structural motif . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Binding experiments show that this motif can interact with the SH 3 domains of p 85 alpha and of c Src . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Only one peptide inhibited binding of Sam 68 to the p85alpha SH 3 domain , whereas several peptides inhibited binding of Sam 68 to c src SH 3 domain , suggesting that Sam 68 uses different proline rich motifs to bind to different SH 3 domains . ^^^ A peptide derived from residues 32 44 of Sam 68 which fits the class 2 SH 3 domain binding consensus sequence inhibited binding of Sam 68 to both p85alpha SH 3 domain and c src SH 3 domain , but with differential potency , suggesting a differential affinity of these SH 3 domains for this proline rich motif . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
In conclusion , our results demonstrate that Gi enables the PDGFR to signal more efficiently to p42 / p44 MAPK , and this appears to be achieved through the regulation of c Src and Grb 2 / PI3K , which are intermediates in the p42 / p44 MAPK cascade . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Here we demonstrate that factor VIIa ( the natural ligand for TF ) induces the activation of the Src family members c Src , Lyn , and Yes , and subsequently phosphatidylinositol 3 kinase ( PI3K ) , followed by stimulation of c Akt / protein kinase B as well as the small GTPases Rac and Cdc 42 . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
A protein ( SNP 70 ) has been isolated that binds to the Src homology domain 3 of p 47 ( phox ) , p85alpha , and c src . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Here we show that gelsolin coprecipitates some of the focal adhesion associated proteins such as c Src , phosphoinositide 3 kinase ( PI3K ) , p 130 ( Cas ) , focal adhesion kinase , integrin alpha ( 5 ) beta ( 3 ) , vinculin , talin , and paxillin . ^^^ Furthermore , lipid extraction of lysates from activated osteoclasts eliminated interaction between gelsolin , c Src , PI3K , and focal adhesion kinase despite equal amounts of gelsolin in both the lipid extracted and unextracted experiment . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The Wiskott Aldrich syndrome protein was identified as a protein that associated selectively with the SH 3 domains derived from c Src , p85alpha , phospholipase Cgamma 1 , and c Fgr . ^^^ Three peptides corresponding to potential Wiskott Aldrich syndrome protein SH 3 domain binding motifs were found to inhibit its association with c Src , Fgr , and phospholipase Cgamma 1 SH3 domains , but not the p85alpha SH 3 domain . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Angiogenic growth factors and their receptors , such as basic fibroblast growth factor ( bFGF ) and Flg , vascular endothelial growth factor ( VEGF ) and Flk 1 , platelet derived growth factor ( PDGF ) B chain and PDGF beta receptor , and five intracellular signal proteins ( phosphatidylinositol 3 kinase [ PI3K ] , phospholipase C gamma [ PLC gamma ] , C Src , SHC , and mitogen activated protein kinase [ MAPK ] ) were examined by Western blot analysis . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Our findings are consistent with a specific regulation of mitogenesis by LMW PTP through a pathway involving c Src kinase but independent by both PI3K and ERK . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The transducers involved in HGF triggered gene inductions were investigated using different protein kinase inhibitors : genistein for the receptor tyrosine kinase , herbimycin A for the nonreceptor tyrosine kinase ( pp 60 ( c src ) ) , wortmannin for phosphatidylinositol 3 kinase ( PI3K ) and H 7 for protein kinase C ( PKC ) . ^^^ The mRNA expression of c jun was likely to undergo a negative regulation through a mechanism involving PI3K , while that of c met seemed to be almost independent from various protein kinases ( PI3K , pp 60 ( c src ) , and PKC ) . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Downregulating PKC delta provides a PI3K / Akt independent survival signal that overcomes apoptotic signals generated by c Src overexpression . 3Y1 rat fibroblasts overexpressing the tyrosine kinase c Src ( 3Y1 ( c Src ) cells ) become transformed by downregulation of protein kinase C delta ( PKC delta ) . ^^^ Collectively , these data indicate that ( 1 ) c Src overexpression renders cells sensitive to apoptotic stress , and ( 2 ) that downregulation of PKC delta provides a novel PI3K / Akt independent survival signal capable of suppressing apoptotic signals . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Erk1 / 2 phosphorylation was insensitive to PTX or H 89 ( PKA inhibitor ) but was inhibited by LY 294002 ( PI3K gamma inhibitor ) , PP 2 ( c Src inhibitor ) , genistein ( tyrosine kinase inhibitor ) and PD 98059 ( MEK inhibitor ) . 6 . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
In conclusion , the adenosine A ( 3 ) receptor recruits a pathway that involves betagamma release from G ( i / o ) , PI3K , Ras , and MEK to induce ERK1 / 2 phosphorylation and activation , whereas signaling is independent of Ca ( 2+ ) , PKC , and c Src . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The main pathway that leads to JNK activation downstream of the EGF receptor involves a sequential activation of c Src and phosphatidylinositol 3 kinase ( PI3K ) . ^^^ The unique pathway elucidated here in which c Src and PI3K are sequentially activated downstream of the EGF receptor may serve as a prototype of signaling mechanisms by GnRHR and by additional GPCRs in various cell types . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Recent evidence suggest that the tyrosine kinase c Src may mediate this proliferative response . c Src can signal through multiple intracellular signaling pathways including ( 1 ) the Shc / Grb2 / ERK2 pathway , ( 2 ) the signal transducers and activators of transcription ( STATs ) , ( 3 ) the focal adhesion kinase ( FAK ) signaling pathway , and ( 4 ) the phosphatidylinositol 3 kinase ( PI3K ) signaling pathway . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Moreover , we show that both c Src / PI3K and c Src / Fak / Erk1 / 2 pathways are involved in the up regulation of c myc and cyclin d 1 expression mediated by PRL . ^^^ The previous findings suggest the existence of two PRL dependent signaling cascades , initiated by the c Src mediated activation of Fak / Erk1 / 2 and PI3K pathways that , subsequently , control the expression of c Myc and cyclin D 1 and the proliferation of T47D and MCF 7 breast cancer cells . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Using pharmacological and genetic inhibitors , we found that inhibition of either c Src or PI3K abolished AMPK that was enhanced by metformin . ^^^ We conclude that activation of AMPK by metformin might be mediated by mitochondria derived RNS , and activation of the c Src / PI3K pathway might generate a metabolite or other molecule inside the cell to promote AMPK activation by the LKB 1 complex . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Tumors exhibited increased association of Egfr with clathrin heavy chain ( CHC ) , Gab 1 , and p85alpha , the regulatory subunit of phosphoinositide 3 kinase ( PI3K ) , and tumors also overexpressed c Src , PDK 1 , and Akt . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
In some contexts , steroid receptors interact directly with c Src and other cytoplasmic signaling molecules , such as Shc , PI3K , and p 130 Cas . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
We also describe the rapid assembly of a membrane associated molecular complex , comprised of ER , c Src and the regulatory unit of phosphatidylinositol 3 kinase ( PI3K ) , p 85 , in response to estrogen . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
In this study , we demonstrate the upregulation of c Src in Raw264 . 7 and peritoneal macrophages ( PEMs ) by LPS , which is inhibited by PP 2 ( an inhibitor for Src family kinases ) , pyrrolidinedithiocarbamate ( PDTC ; NF kappaB inhibitor ) and LY 294002 ( PI3K inhibitor ) . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
These data indicate that calcium activates PLC gamma 1 via increased PIP 3 formation mediated by c src and fyn activated PI3K . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Thus IL 18 induced CXCL 16 expression via a MyD 88 > IRAK 1 IRAK4 TRAF 6 ( tumor necrosis factor receptor associated factor 6 ) > c Src > PI3K > Akt > JNK > AP 1 pathway . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The goal of this study was to test the hypothesis that the phospholipase C ( PLC ) / protein kinase C ( PKC ) / c src / phosphatidylinositol 3 kinase ( PI3K ) pathway contributes to the vascular angiotensin II / alpha ( 2 ) adrenoceptor interaction . ^^^ Intrarenal infusions of U 73122 [ 1 [ 6 [ [ ( 17beta ) 3 methoxyestra 1 , 3 , 5 ( 10 ) trien 17 yl ] amino ] hexyl ] 1H pyrrole 2 , 5 dione ; 3 microg / min ; PLC inhibitor ] , GF109203X [ bisindolylmaleimide 1 ; 10 microg / min ; PKC inhibitor ] , CGP 77675 [ 1 ( 2 { 4 [ 4 amino 5 ( 3 methoxyphenyl ) pyrrolo [ 2 , 3 d ] pyrimidin 7 yl ] phenyl } ethyl ) piperidin 4 ol ; 5 microg / min ; c src inhibitor ] , and wortmannin ( 1 microg / min ; PI3K inhibitor ) abolished the angiotensin II / alpha ( 2 ) adrenoceptor interaction . ^^^ Preglomerular microvascular smooth muscle cells expressed phospholipase ( PLC ) beta ( 2 ) , PLC beta ( 3 ) , c src , phospho ( tyrosine 416 ) c src , and PI3K . ^^^ In conclusion , the PLC / PKC / c src / PI3K pathway may contribute importantly to the interaction between alpha ( 2 ) adrenoceptors and angiotensin 2 on renal vascular resistance . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Therapeutic maneuvers may target receptor tyrosine kinases ( EGFR , VEGFR , FGFR ) , chemokines or G protein coupled receptors ( CXCR 4 , CXCR 2 , EphB 2 ) , hypoxia inducible factor ( HIF ) , and signaling pathways ( c Src , PI3K , Akt , chaperon complexes ) in tumor cells . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Therefore , we suggest a redox circuit whereby , upon PDGF stimulation , PKC , PI3K and NADPH oxidase activity contribute to complete c Src kinase activation , thus promoting maximal phosphorylation and activation of PDGFr tyrosine phosphorylation . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Inhibition of c Src or phosphoinositide 3 kinase ( PI3K ) with PP 2 or wortmannin , respectively , abolished ouabain induced downregulation of NHE 3 activity and mRNA expression . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Using biochemical and genetic approaches , we demonstrate that TLR 2 ligands stimulate release of Ca ( 2+ ) from intracellular stores by activating TLR 2 phosphorylation by c Src , and recruiting PI3K and phospholipase Cgamma to affect Ca ( 2+ ) release through inositol ( 1 , 4 , 5 ) trisphosphate receptors . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
METHODS : Using the human colonic tumour cell line HCT 116 as a model , we first measured the activation of PI3K , p 60 Src and JAK 2 in response to G gly by in vitro kinase assays . ^^^ RESULTS : G gly stimulation induced p 60 Src , JAK 2 and PI3K activation in HCT 116 . ^^^ CONCLUSION : Our results suggest that the p 60 Src / PI3K and JAK2 / PI3K pathways act independently to mediate G gly proliferative effect on human colonic tumour cells . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
In contrast , only the p 85 alpha subunit was detectably phosphorylated when PI 3 K was associated with mT : cSrc . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Furthermore , we show an interaction between cSrc and the p 85 regulatory subunit of PI3K in infected cells through a phosphorylation dependent mechanism . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The p 85 alpha subunit of PI 3 ' kinase contains two Src homology ( SH ) 2 domains , which are implicated in the interactions of signalling proteins with activated receptors . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Co expression studies in insect cells have shown that p 85 alpha and p 85 beta are substrates for the protein tyrosine kinases of epidermal growth factor , colony stimulating factor 1 and c erbB 2 receptors and the src family kinase p59c fyn . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The interactions of the phosphotyrosine ( Tyr ( P ) ) containing proteins in basal and insulin stimulated 3T3 L 1 adipocytes with src homology 2 ( SH 2 ) domains from phosphatidylinositol 3 kinase ( PI3K ) , ras GTPase activating protein ( GAP ) , and phospholipase C gamma have been examined . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The latter was found to undergo specific association with the p 85 alpha regulatory subunit of PI3K but not with two other proteins that contain src homology domains . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Amino acid sequence analysis and cDNA cloning reveals two related 85 kd proteins ( p 85 alpha and p 85 beta ) , which both contain one SH 3 and two SH 2 regions ( src homology regions ) . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
We previously showed by M 13 phage display that the Src , Fyn , Lyn , and phosphatidylinositol 3 kinase ( PI3K ) SH 3 domains preferred the same class 1 type core binding sequence , RPLPP psi P . ^^^ These libraries were screened for binding to the Src , Fyn , Lyn , Yes , and PI3K SH 3 domains . ^^^ The amino acids selected in the flanking sequences were similar for Src , Fyn , and Yes SH 3 domains ; however , Lyn and PI3K SH 3 domains showed distinct binding specificities . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
In this report , we demonstrate that Raf 1 associated with the SH 2 domain of Fyn ( a member of the Src tyrosine kinase family ) but not with the SH 2 domains of phospholipase C gamma 1 , the p 85 alpha subunit of phosphatidylinositol 3 kinase , and SH 2 containing protein tyrosine phosphatase 2 . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
In addition , we show that PtdIns 3 kinase is significantly activated by the p125FAK proline rich sequence binding to the src homology 3 domain of p 85 alpha subunit . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The pro 4 / pro 5 motif of Shb binds in vitro particularly well to the Src , p 85 alpha PI 3 kinase and Eps 8 SH3 domains expressed as GST fusion proteins . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The results suggest that while the overall structures of the binding sites in the PI3K and Src SH 3 domains are similar , their ligand binding properties may differ . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The p 85 alpha subunit contains a NH 2 terminal src homology ( SH ) 3 domain , a region with homology to the product of the breakpoint cluster region ( bcr ) gene , and a COOH terminal portion of the molecule which contains two SH 2 domains , separated by a spacer region . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Src phosphorylation of the epidermal growth factor receptor at novel sites mediates receptor interaction with Src and P 85 alpha . ^^^ The sequences surrounding Tyr 891 and Tyr 920 match the reported consensus binding sequences for the SH 2 domains of Src and the regulatory domain of phosphatidylinositol 3 kinase ( p 85 alpha ) , respectively . ^^^ Upon EGF treatment of MCF 7 or three colorectal carcinoma cell lines ( WiDr , DLD 1 , and LS174T ) , the EGF R coimmunoprecipitated with both p 85 alpha and Src . ^^^ These data demonstrate that EGF R is phosphorylated in vivo at non autophosphorylation sites and that these novel sites can act as docking sites for Src , P 85 alpha , and potentially other SH 2 containing proteins . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Identification of Src , Fyn , Lyn , PI3K and Abl SH 3 domain ligands using phage display libraries . ^^^ We have employed a novel modification of phage display involving biased libraries to identify peptide ligands of the Src , Fyn , Lyn , PI3K and Abl SH 3 domains . ^^^ The Src SH 3 domain prefers the sequence XXXRPLPPLPXP , Fyn prefers XXXRPLPP ( I / L ) PXX , Lyn prefers RXXRPLPPLPXP , PI3K prefers RXXRPLPPLPP while the Abl SH 3 domain selects phage containing the sequence PPPYPPPP ( I / V ) PXX . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
In addition OM can stimulate the in vivo activation of PI3K and increases the PI3K activity in anti phosphotyrosine and anti src kinase family antibody directed immunoprecipitates . ^^^ These data suggest that in KS cells OM can stimulate formation of tyrosine kinase co ordinate signalling complexes , containing at least src kinase family and PI3K , which can drive the accumulation of the putative second messengers D 3 phosphorylated phosphoinositides . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
We have used a transient expression system and mutant platelet derived growth factor ( PDGF ) receptors to study the binding specificities of the Src homology 2 ( SH 2 ) regions of the Ras GTPase activator protein ( GAP ) and the p 85 alpha subunit of phosphatidylinositol 3 kinase ( PI 3 kinase ) . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Crystal structures of the amino terminal SH 2 domain of the p85alpha subunit of phosphatidylinositol ( PI ) 3 kinase , alone and in complex with phosphopeptides bearing pTyr Met / Val Xaa Met motifs , show that phosphopeptides bind in the two pronged manner seen in high affinity Lck and Src SH 2 complexes , with conserved interactions between the domain and the peptide segment from phosphotyrosine to Met+3 . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
One form is identical to p85alpha throughout the region which encodes both Src homology 2 ( SH 2 ) domains and the inter SH 2 domain / p110 binding region but diverges in sequence from p85alpha on the 5 ' side of nucleotide 953 , where the entire break point cluster gene and SH 3 regions are replaced by a unique 34 amino acid N terminus . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Purified amino terminal Src homology 2 ( SH 2 ) domains of GAP , PLCgamma 1 and the p85alpha subunit of PI 3 kinase , as well as the carboxy terminal SH 2 domain of the latter protein and the unique SH 2 domain of Grb 2 , were injected into full grown , stage 6 Xenopus laevis oocytes . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Following binding of platelet derived growth factor ( PDGF ) , the PDGF alpha receptor ( alphaPDGFR ) becomes tyrosine phosphorylated and associates with a number of signal transduction molecules , including phospholipase Cgamma 1 ( PLCgamma 1 ) , phosphatidylinositol 3 kinase ( PI3K ) , the phosphotyrosine phosphatase SHP 2 , Grb 2 , and Src . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The mammalian phosphoinositide 3 kinases ( PI3Ks ) p110alpha , beta , and delta form heterodimers with Src homology 2 ( SH 2 ) domain containing adaptors such as p85alpha or p 55 ( PIK ) . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The presence of a type 1 ' turn in the BG loop , which is dependent on the presence of a glycine residue at position BG 3 , is indicative of a binding pocket , characteristic of the Src family , SykC and Abl , rather than a binding groove found in PLC gamma 1C , p 85 alpha N and Shc , for example . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The region between the Src homology 2 ( SH 2 ) domains of p55PIK bound to the NH 2 terminus region of p110alpha , as previously shown for p85alpha . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
In particular , the C SH 2 structure is very similar to both the p 85 alpha N terminal SH 2 domain ( N SH 2 ) and the Src SH 2 domain with a root mean square difference ( rmsd ) for 44 C alpha atoms of 1 . 09 and 0 . 89 A , respectively . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The putative hp 55 gamma protein is composed of a unique amino terminal region followed by a proline rich motif and two Src homology 2 ( SH 2 ) domains , which are highly homologous to those in mouse p55PIK , rat p 55 gamma , human p 85 alpha and bovine p 85 beta ; it contains no SH 3 domain . hp 55 gamma mRNAs are expressed in most human fetal and adult tissues with particularly high abundance in adult testis . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
In addition to inhibitors of tyrosine kinase [ tyrphostin 47 / AG213 , genistein and the src selective inhibitor CP 118 , 556 / PP1 ] , cyclooxygenase ( indomethacin , INDO ) and diacylglycerol lipase ( U 57 , 908 ) , we also used the signal pathway probe inhibitors of mitogen activated protein kinase kinase ( MEK : PD 98059 ) , phosphatidylinositol 3 ' kinase [ PI3K : Wortmannin ( WM ) and LY 294002 ] , protein kinase C [ PKC : GF109203X ( GF ) ] , and of the EGF receptor kinase ( PD 153035 ) . ^^^ We conclude that protease activated receptor no . 1 ( thrombin receptor ) mediated contractions in the logitudial muscle , like EGF receptor activated responses , require the influx of extracellular calcium and use parallel signal pathways upstream of the cyclooxygenase step , involving MEK , PI3K , kinase C and possibly cellular src . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Employing antibodies specific to two p 85 isoforms , p85alpha and p85beta , we demonstrate that HTC IR cells express both p 85 isoforms , and these isoforms induce the formation of similar signaling complexes in response to insulin . p 60 70 , present in both alpha p85alpha and alpha p85beta immunoprecipitates , is a GAP associated protein , but is distinct from the p 68 src associated protein in mitosis ( Sam 68 ) by several criteria . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Engagement of CD 28 leads to its tyrosine phosphorylation and subsequent binding to Src homology 2 ( SH 2 ) containing proteins including the p 85 subunit of phosphatidylinositol 3 ' kinase ( PI3K ) ; however , the contribution of PI3K to CD 28 dependent costimulation remains controversial . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
At the same time , expression of Syk resulted in the activation dependent phosphorylation of three proteins that bound to the src homology 2 ( SH 2 ) domains of PI3K p 85 . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
It has been demonstrated that the lipid products of the phosphoinositide 3 kinase ( PI3K ) can associate with the Src homology 2 ( SH 2 ) domains of specific signaling molecules and modify their actions . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Ligation of the TCR or CD 28 induces activation of phosphatidylinositol 3 kinase ( PI3K ) , the TEC family protein tyrosine kinase , EMT / ITK / TSK ( EMT ) , and the SRC family tyrosine kinase , LCK . ^^^ Fusion proteins containing the SRC homology 2 domain of EMT interact with PI3K or a PI3K associated molecule in a tyrosine phosphorylation dependent manner . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
In pp 125 ( FAK ) expressing cells , this was concomitant with increased association of IRS 1 with Src homology 2 containing proteins such as growth factor receptor bound protein 2 , phosphatidylinositol ( PI ) 3 kinase p85alpha subunit , and Src homology 2 containing protein tyrosine phosphatase 2 . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Here we show that p85alpha , the regulatory subunit of PI 3 kinase , specifically associates through its Src homology 2 domains with tyrosine phosphorylated IkappaB alpha in vitro and in vivo after stimulation of T cells with pervanadate . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
This residue was known to serve as a binding site for both Src and phosphatidylinositol 3 kinase ( PI3K ) , implying that either one or both are required for FAK to promote cell migration . ^^^ Furthermore , a FAK mutant capable of binding Src but not PI3K was generated by a substitution of Asp residue 395 with Ala . ^^^ Together , these results strongly suggest that PI3K binding is required for FAK to promote cell migration and that the binding of Src and p 130 ( Cas ) to FAK may not be sufficient for this event . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Structural and biochemical evaluation of the interaction of the phosphatidylinositol 3 kinase p85alpha Src homology 2 domains with phosphoinositides and inositol polyphosphates . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
We have previously demonstrated that both Gas 6 mitogenic and survival effects are mediated by Src and the phosphatidylinositol 3 OH kinase ( PI3K ) . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
These events are preceded by the ligand induced tyrosine phosphorylation of the receptor and its association with SH 2 containing signaling enzymes including Src family members ( Src ) , the phosphotyrosine phosphatase SHP 2 , phosphatidylinositol 3 kinase ( PI3K ) , and phospholipase C gamma 1 ( PLCgamma ) . ^^^ In contrast , multiple signaling enzymes were required for maximal chemotaxis , as receptors unable to associate with either Src , PI3K , or PLCgamma initiated chemotaxis to 4 , 47 , or 56 % of the wild type level , respectively . ^^^ We conclude that for the alphaPDGFR , PI3K plays a major role in initiating DNA synthesis , whereas PI3K , PLCgamma , and especially Src are required for chemotaxis . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
This process has been proposed to be mediated by an interaction between the Src family kinase LYN and the p 85 subunit of PI3K and / or through p 85 membrane recruitment mediated by CBL and / or CD 19 . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
PI3K itself possesses oncogenic activity and also forms complexes with some viral or cellular oncoproteins ( src , ras , rac , alb , T antigen ) , whose transforming activities are realized only in presence of PI3K . ^^^ The transforming effect of PI3K is supposed to occur on the basis of complex alterations in cellular signaling pathways : appearance of constitutively generated PI3K dependent mitogen signal and activation of some protooncogenes ( src , ras , rac , etc . ) , PI3K / PKB pathway stimulation resulting in delay of apoptosis and increase of cell survival , and actin cytoskeleton reorganization . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Autophosphorylation of the platelet derived growth factor ( PDGF ) receptor triggers intracellular signaling cascades as a result of recruitment of Src homology 2 domain containing enzymes , including phosphatidylinositol 3 kinase ( PI3K ) , the GTPase activating protein of Ras ( GAP ) , the protein tyrosine phosphatase SHP 2 , and phospholipase C gamma 1 ( PLC gamma 1 ) , to specific phosphotyrosine residues . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Indeed , three amino acids important for ligand binding in Src SH 3 were replaced in the Slap SH 3 sequence ; Slap SH 3 did not bind to the Src SH 3 partners p85alpha , Shc , and Sam 68 in vitro , and the chimeric tyrosine kinase Slap / SrcK , composed of SlapDeltaC fused to the SH 2 linker kinase sequence of Src , was not regulated in vivo . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NGF induced activation of PKC iota was observed to be dependent on phosphatidylinositol 3 kinase ( PI3K ) and led to coassociation of PKC iota with Ras and Src . ^^^ Src , PI3K , and PKC iota were likewise required for NGF induced NF kappaB activation and cell survival , whereas Ras was not required for either survival or NF kappaB activation but was required for differentiation . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The Ras activity was promoted by three upstream effectors , growth factor bound protein 2 ( Grb 2 ) , phosphatidylinositol 3 kinase ( PI3K ) and Src cytoplasmic kinase . ^^^ Ras activation was inhibited by a Grb 2 dominant negative form ( P49L ) , by PI3K inhibitors , including wortmannin , LY 294002 , the N SH 2 domain of p85alpha PI3K and by the SH 2 domain of Src . ^^^ It emphasizes the role played by PI3K and Src and their connections with the Ras cascade in the FGFR 1 signal transduction . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
This is mediated by binding of the Src homology ( SH ) 2 domains in PI3K to phosphotyrosine containing sequences on membrane associated docking proteins . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Here we investigate the requirement of MAP ( MAPK ) and phosphatidylinositol 3 ( PI3K ) kinases in the transformation of rat intestinal epithelial ( RIE ) cells by oncogenic forms of insulin receptor ( gag IR ) , insulin like growth factor 1 receptor ( gag IGFR ) , and 5 Src . ^^^ However , at concentrations of LY 294002 where activated forms of Akt , a downstream component of the PI3K pathway , were undetectable , colony and focus forming abilities of the 5 Src RIE cells were only slightly affected whereas those of gag IR / IGFR RIE cells were greatly inhibited . ^^^ Similarly , rapamycin , known to inhibit p70S6 kinase , a downstream component of the PI3K Akt pathway , also inhibited gag IR / IGFR induced , but not 5 Src induced , focus and colony formation . ^^^ We conclude that the MAPK and PI3K signaling pathways are differentially required for transformation of RIE cells by oncogenic IR and IGFR versus Src and the pattern of requirements is different from that of fibroblast transformation . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The ability of FAK to mediate integrin signaling in the regulation of cell cycle progression depends on the phosphorylation of Tyr 397 , which implies a functional significance for the formation of FAK signaling complexes with Src , phosphatidylinositol 3 kinase ( PI3K ) and Grb 7 . ^^^ We have previously described a FAK mutant , D395A , that selectively disrupts FAK binding to PI3K , but allows FAK association with Src . ^^^ Using this mutation in a mislocalized FAK mutant background , we show here that formation of a FAK / PI3K complex is not sufficient for cell cycle progression but the formation of a FAK / Src complex plays an essential role . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The N terminal src homology 2 ( SH 2 ) domain of the p 85 subunit of phosphoinositide 3 kinase ( PI3K ) has a higher affinity for a peptide with two phosphotyrosines than for the same peptide with only one . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Herbimycin A abolished phosphotransferase activities of the Src kinase following stimulation with CCK , whereas wortmannin had no effect , suggesting that Src is an upstream regulator of PI3K . ^^^ Immunoprecipitation studies using an anti Src antibody ( clone CD 11 ) or PI3K antibody in conjunction with the anti phosphotyrosine antibody showed that , in response to CCK , tyrosine phosphorylations of Src and PI3K were enhanced at the location of p 60 and p 85 , respectively . ^^^ Src was co immunoprecipitated with PI3K following stimulation with CCK , suggesting that pp60src forms an immunocomplex with PI3K via the N SH 2 domain of the p 85 regulatory subunit . ^^^ Thus PI3K and its association with Src appear to be involved in mediating CCK stimulated pancreatic exocytosis . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
To elucidate a role of the Src homology 3 ( SH 3 ) conserved acidic residue Asp 21 of the phosphatidylinositol 3 kinase ( PI3K ) SH 3 domain , structural changes induced by the D21N mutation ( Asp 21 > Asn ) were examined by circular dichroism ( CD ) and nuclear magnetic resonance ( NMR ) spectroscopies . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Nicotine induced protection was suppressed by an alpha 7 nicotinic receptor antagonist ( alpha bungarotoxin ) , a phosphatidylinositol 3 kinase ( PI3K ) inhibitor ( LY 294002 and wortmannin ) , and a Src inhibitor ( PP 2 ) . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
These events are dependent on the Shc / Grb2 / Ras pathway , on Src and PI3Kinase ( PI3K ) , as shown by the use of SH 2 domains or dominant negative proteins , and on PLC gamma and calcium as demonstrated by a PLC gamma inhibitory peptide and BAPTA AM . ^^^ This study shows that the transduction cascades induced by FGF 1 on FGFRs from MDA MB 231 cells represent the sum of Ras , Src , PI3K , and PLC gamma pathways . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Differential regulation of cell migration and cell cycle progression by FAK complexes with Src , PI3K , Grb 7 and Grb 2 in focal contacts . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Recent data from mice deficient for phosphatase and tensin homologue deleted from chromosome 10 or src homology 2 domain containing 5 ' inositol phosphatase , phosphatases that negatively regulate the phosphatidylinositol 3 kinase ( PI3K ) pathway , revealed an increased number of macrophages in these animals , suggesting an essential role for the PI3K pathway for macro phage survival . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
This includes the protein tyrosine kinases Src , Hck , and Fyn , the p85alpha regulatory subunit of phosphatidylinositol 3 kinase , phospholipase Cgamma , and the adaptor protein Grb 2 . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
DAPP 1 ( dual adaptor for phosphotyrosine and 3 phosphoinositides 1 ) is a broadly distributed pleckstrin homology ( PH ) and Src homology 2 domain containing protein that can bind phosphatidylinositol 3 , 4 , 5 trisphosphate ( PtdIns ( 3 , 4 , 5 ) P ( 3 ) ) and can be phosphorylated on tyrosine 139 and internalised in response to activation of type 1 phosphoinositide 3 kinases ( PI3K ) . ^^^ In endothelial cells overexpressing wild type platelet derived growth factor beta ( PDGFbeta ) receptors , which express Bmx and Src as their major Btk ( Bruton ' s tyrosine kinase ) family and Src family tyrosine kinases , respectively , PDGF can stimulate PI3K dependent tyrosine phosphorylation of DAPP 1 . ^^^ We conclude that Src family kinases are responsible for tyrosine phosphorylation of DAPP 1 in vivo and that PI3K regulation is at the level of PH domain mediated translocation of DAPP 1 to PI3K products in the membrane . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Specific binding of the C terminal Src homology 2 domain of the p85alpha subunit of phosphoinositide 3 kinase to phosphatidylinositol 3 , 4 , 5 trisphosphate . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
In vitro binding experiments proved that glutathione S transferase p85alpha N or C terminal SH 2 domains independently bound to erythropoietin receptor , which was tyrosine phosphorylated by Src . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The Src homology 2 ( SH 2 ) domain of the phosphatidylinositol 3 kinase ( PI3K ) regulatory subunit binds Gab 1 in a phosphorylation independent manner . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
To investigate whether another signaling pathway is involved , the src kinase inhibitor PP 2 and the phosphoinositol 3 kinase inhibitor ( PI3K ) , LY 294002 , were used . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Experiments with Src , p85alpha and Akt dominant negative forms indicate that in oestradiol treated cells these signalling effectors target the cyclin D 1 promoter . ^^^ In turn , stimulation of Src activity is abolished in ERalpha expressing NIH 3T3 fibroblasts by co transfection of the dominant negative p85alpha and in MCF 7 cells by the PI 3 kinase inhibitor , LY 294002 . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
PymT , a membrane associated scaffold , recruits and activates Src family tyrosine kinases , and , once tyrosine phosphorylated , binds proteins with PTB and SH 2 domains such as ShcA , phosphatidylinositol 3 kinase ( PI3K ) and phospholipase Cgamma 1 ( PLCgamma 1 ) . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Taken together , our results demonstrate a critical role for Src kinases in regulating neutrophil cytotoxic effector functioning through PI3K PKB . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
We have generated knockin mice harboring mutations in the PDGFalpha receptor ( PDGFalphaR ) that selectively eliminate its capacity to activate PI 3 kinase ( alpha ( PI3K ) ) or Src family kinases ( alpha ( Src ) ) . ^^^ The alpha ( PI3K ) mutation leads to neonatal lethality due to impaired signaling in many cell types , but the alpha ( Src ) mutation only affects oligodendrocyte development . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
We have explored this signalling in transformed cells . 5 Src and K Ras activate PI3K and PLC , as demonstrated by in situ production of the corresponding lipid products . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
These potential targets include Src homology 2 domain containing inositol 5 phosphatase 2 ( SHIP 2 ) , phosphatase and tensin homolog deleted on chromosome ten ( PTEN ) , kappaB kinase beta ( IKKbeta ) , PKC isoforms , and the PI3K p 85 subunit . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
This FAK phosphorylation needs activation of the Src family tyrosine kinase ( s ) for which the 5 Crk SH 2 domain is responsible . 5 Crk was unable to activate the PI3K / AKT pathway in FAK null cells , indicating the functional importance of FAK . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The cross talk between bombesin and beta 1 integrin engaged signals seems to be crucial for the modulation of both membrane linked uPA activity and MMP 9 activation and triggers complex intracellular signaling pathways requiring activation of tyrosine kinase activity , including that of src and PI3K . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
We analyzed the signal transduction pathways regulating bud development using inhibitors of protein kinase C , Src , PI3K and ERK . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
To investigate how aromatic residues contribute to ligand recognition , circular dichroism ( CD ) and 235 nm excited ultraviolet resonance Raman spectroscopies have been applied to Src and phosphatidylinositol 3 kinase ( PI3K ) SH3s . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
In this study , we show that sE selectin is a potent mediator of human dermal microvascular endothelial cell ( HMVEC ) chemotaxis , which is predominantly mediated through the Src and the phosphatidylinositiol 3 kinase ( PI3K ) pathways . ^^^ HMVECs pretreated with the Src inhibitor ( PP 2 ) and the PI3K inhibitor ( LY 294002 ) or transfected with Src antisense oligonucleotides or Akt dominant negative mutants significantly inhibited sE selectin mediated HMVEC tube formation . ^^^ Similarly , in the Matrigel plug in vivo assay , sE selectin induced a 2 . 2 fold increase in blood vessel formation , which was significantly inhibited by PP 2 and LY 294002 but not by PD 98059 . sE selectin induced a marked increase in Src , ERK1 / 2 , and PI3K phosphorylation . ^^^ PI3K and ERK1 / 2 phosphorylation was significantly inhibited by PP 2 , thereby suggesting that both of these pathways may be activated via Src kinase . ^^^ Taken together , our data clearly show that sE selectin induced angiogenesis is predominantly mediated through the Src PI3K pathway . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
However , PI3K can not account for the Src independent pathway , since simultaneous inhibition of both PI3K and Src did not completely block effects of R Ras on FAK phosphorylation . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
In summary , CO 2 stimulation of NBC is mediated at least in part by increased immunoreactive NBC protein in the basolateral membrane , a process which requires the interaction of PI3K with Src family kinase . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Specific inhibitors of protein kinase C ( PKC ) , Src , and phosphatidylinositol 3 kinase ( PI3K ) inhibit Par 1 induced VEGF expression , suggesting the participation of these kinases in the process . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Additionally , muscarinic receptors in PFC slices activated PKC and the focal adhesion kinase Pyk 2 ( a potential molecular link between PKC and Src ) in a PI3K dependent manner . ^^^ Together , our results show that mAChR activation in PFC pyramidal neurons enhances GABA ( A ) receptor functions through a PKC dependent , Src mediated signaling cascade that is gated by an insulin / PI3K pathway . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
METHODS : Human mesangial cells were exposed to IGF 1 in the presence and in the absence of ( 1 ) anti IGF 1 type 1 receptor antibody ( alpha IR 3 ) ( 1 microg / mL ) , a monoclonal antibody blocking the IGF 1 type 1 receptor ; ( 2 ) wortmannin ( 600 nmol / L ) , a phosphatidylinositol 3 kinase ( PI3K ) inhibitor ; ( 3 ) 4 amino 5 ( 4 chlorophenyl ) 7 ( t butyl ) pyrazolo [ 3 , 4 d ] pyrimidine ( PP 2 ) , a specific Src inhibitor ( 10 micromol / L ) ; and ( 4 ) cyclic stretch ( approximately 10 % elongation ) . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
BRL 37344 stimulated proliferation , which could be blocked by inhibitors of Src , PI3K , and MEK . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Moreover , chemotactic action of PS G requires the activities of PI3K , p 38 MAPK , Src tyrosine kinases and PKC . 6 All these results demonstrate the abilities of PS G to enhance neutrophil function in phagocytosis and chemotaxis , and further provide evidence to strengthen the beneficial remedy of G . lucidum in human to enhance defense system . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Our results show that even though the ICOS Src homology ( SH ) 2 binding domain strongly activated PI3K , it was unable to substitute for the CD 28 SH2 binding domain to induce high levels of IL 2 and Bcl 10 ( L ) . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Our results point to the involvement of several ErbB specific ligands ( amphiregulin and neuregulin 1 ) and enzymes or adaptor molecules ( PI3K , Src , Shc and Grb 7 ) in the ErbB pathway dysregulation associated with breast cancer . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
We demonstrate , herein , that Src kinases regulate the phosphatidylinositol 3 kinase ( PI3K ) signaling cascade via altering the function of the PTEN tumor suppressor . ^^^ Overexpression of activated Src protein tyrosine kinases in PTEN deficient breast cancer cells does not alter AKT phosphorylation , an indicator of signal transduction through the PI3K pathway . ^^^ Taken together , the data indicate that activated Src inhibits PTEN function leading to alterations in signaling through the PI3K / AKT pathway . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Using panels of relatively specific kinase inhibitors , antisense oligonucleotides , and dominant negative mutants , we show that mitogen activated protein kinase ( MAPK ) and phosphatidylinositol 3 kinase ( PI3K ) are critical for MIF dependent HMVEC migration , whereas Src and p 38 kinases are nonessential . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Here we demonstrate that PI3K activation by Reelin requires Src family kinase activity and depends on the Reelin triggered interaction of Dab 1 with the PI3K regulatory subunit p85alpha . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Activation of PI3K / Akt by androgen was inhibited by dominant negative Src . ^^^ Neither N terminal truncated nor proline rich region deleted AR mutants , which are unable to bind to p85alpha and Src , respectively , was able to mediate androgen induced PI3K / Akt activation . ^^^ These findings indicate that a triple complex between AR , p85alpha , and Src is required for androgen stimulated PI3K / Akt activation , and that the PI3K / Akt pathway , in addition to mitogen activated protein kinase , mediates androgen induced cell growth and cell survival . . ^^^ Activation of phosphatidylinositol 3 kinase / Akt pathway by androgen through interaction of p85alpha , androgen receptor , and Src . ^^^ The sites of interaction on the two proteins were mapped to the C terminal Src homology 2 domain of p85alpha and N terminus of AR . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
In brown adipocytes expressing the IRS 3F4 mutant , the association of the p85alpha regulatory subunit via Src homology 2 binding was lost , but insulin nevertheless induced PI 3 kinase activity and Akt phosphorylation in a wortmannin dependent manner . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Human retinal endothelial cells were stimulated with an Eph B4 / Fc chimera and probed for phosphorylation of phosphatidylinositol 3 kinase ( PI3K ) , Src , and mitogen activated protein kinase ( MAPK ) pathways . ^^^ Treatment with EphB4 / Fc chimera resulted in activation of PI3K , Src , and MAPK pathways . ^^^ Blockade of Src PI3K pathways produced significant attenuation of Eph B4 / Fc stimulated migration . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
We conclude that MBP stimulates a Src kinase dependent activation of class 1 ( A ) PI3K and , in turn , activation of PKCzeta in neutrophils , which contributes to the activation of NADPH oxidase and the resultant O ( 2 ) ( ) production in response to MBP stimulation . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Previous genetic analysis has characterized mutants of the N terminal src homology 2 ( SH 2 ) domain of the p 85 subunit of phosphoinositide 3 kinase ( PI3K ) . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Protein and DNA synthesis were dependent on activation of Jak / STAT , MEK1 / 2 , PI3K and Src pathways as evidenced by decreased 3H leucine and 3H thymidine incorporation after pretreatment with AG 490 , PD 98059 , LY 294002 and genistein respectively . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Taken together , these data support a role for TGF beta 1 activation of two distinct pathways ( Src MAPK PI3K NF kappaB dependent and Src MAPK AP 1 dependent ) for TGF beta 1 dependent uPA up regulation and promotion of invasion . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
We investigated whether phosphatidylinositol 3 kinase ( PI3K ) and 68 kDa Src associated during mitosis ( SAM 68 ) are involved in angiotensin 2 ( ANG 2 ) growth signaling in vascular smooth muscle cells ( VSMCs ) from spontaneously hypertensive rats ( SHR ) . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
In this study , we further demonstrate that DcR 3 is able to induce actin reorganization and enhance the adhesion of monocytes and THP 1 cells by activating multiple signaling molecules , such as protein kinase C ( PKC ) , phosphatidylinositol 3 kinase ( PI3K ) , focal adhesion kinase ( FAK ) and Src kinases . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
We report here that NS5A binds directly to the Src homology 3 domain of the p 85 regulatory subunit of phosphoinositide 3 kinase ( PI3K ) , and this interaction is mediated by a novel ( non proline rich ) motif within NS5A . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
We show that phosphorylation at these residues is not due to auto phosphorylation , but requires instead Src family kinase and phosphatidylinositol 3 kinase ( PI3K ) activities . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
We also show that Src directed activation of insulin receptor substrate 1 , phosphatidylinositol 3 kinase ( PI3K ) , Akt , and Bad phosphorylation conform a substantial component of the survival route because pharmacological inhibition of PI3K and Akt canceled the antiapoptotic effects of NO . ^^^ In addition , we found that NO produces c Src / PI3K and PKG dependent activation of ERK 1 / 2 . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The myeloproliferative disorder of mice lacking the Src homology 2 ( SH 2 ) containing 5 ' phosphoinositol phosphatase , SHIP , underscores the need for closely regulating phosphatidylinositol 3 kinase ( PI3K ) pathway activity , and hence levels of phosphatidylinositol species during hematopoiesis . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Pharmacological inhibition of either phosphatidylinositol 3 kinase ( PI3K ) or src family kinases prevented both ephrinA 5 mediated and slit 2 mediated growth cone collapse . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Results with specific inhibitors of signal transduction pathways suggest that extracellular and intracellular calcium , PI3K and a Src family kinase are involved in the BzATP induced Akt phosphorylation pathway . 5 . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The Src homology domain 2 ( SH 2 ) containing tyrosine phosphatase SHP 2 has been implicated in the regulation of the phosphatidylinositol 3 ' kinase ( PI3K ) / Akt pathway . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Epo independent terminal differentiation as well as normal Epo induced differentiation were repressed by inhibitors of JAK 2 ( AG 490 ) , PI3K ( LY 294002 ) , and the Src family kinases ( PP 2 ) . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
These findings defined a PRL signalling cascade in W 53 cells , involving Src kinases / PI3K / Akt / FKHRL1 GSK 3 , that mediates stimulation of c Myc expression . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Inhibition of src family tyrosine kinase or PI3K activity blocked pMHC tetramer and anti CD 3 stimulated adhesion . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
This up regulation on T cells can be partially inhibited by reagents that block the activity of src family kinases , calcineurin , MEK , or PI3K . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
These results indicate that a major pathway for adhesion dependent activation of PI3K / Akt is triggered by the membrane proximal part of the beta 1 subunit in a FAK and Src independent manner . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Whereas protein kinase A inhibitor H 8 and protein kinase C inhibitor bisindolymaleimide did not block the T 3 induced increase in Na , K ATPase activity , two inhibitors of phosphoinositide 3 kinase ( PI3K ) , wortmannin and Ly 294002 , and two Src kinase inhibitors , PP 1 and PP 2 , blocked the T 3 induced Na , K ATPase activity . ^^^ Transient expression of a constitutively active Src kinase increased Na , K ATPase activity , PI3K activity , and phosphorylation of PKB / Akt at serine 473 . ^^^ PP 1 or PP 2 blocked T 3 stimulated PKB / Akt phosphorylation at serine 473 and PI3K activity that was activated by an active mutant of Src ; however , wortmannin did not inhibit the T 3 stimulated Src kinase activity . ^^^ Although PP 1 and wortmannin abolished the increase in Na , K ATPase activity induced by the active mutant of Src , PP 1 did not inhibit the active mutant of PI3K up regulated Na , K ATPase activity . ^^^ In summary , T 3 stimulates the PI3K / PKB pathway via the Src family of tyrosine kinases , and activation of both the Src family kinases and PI3K is required for the T 3 induced stimulation of Na , K ATPase activity and its cell surface expression in adult rat alveolar epithelial cells . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
In the cells treated with CGS 21680 , PI3K activation was prevented either by inhibiting adenylate cyclase and PKA with , respectively , 2 , 5 dideoxyadenosine and H 89 or by blocking Galphai protein and Src tyrosine kinase with , respectively , pertussis toxin and PP 2 . ^^^ This suggested that PKA phosphorylated adenosine A 2A receptors may activate PI3K by coupling it with Galphai protein through Src . ^^^ CONCLUSIONS : PI3K is activated following hepatocyte hypoxic preconditioning by the combined stimulation of adenosine A 2A receptors , PKA , Galphai protein , and Src . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
In conclusion , TGF beta 1 dependent activation of Smad2 / 3 , leading to PAI 1 synthesis , may be negatively regulated by Src , but not its downstream targets MAPK and PI3K in SKOV 3 cells . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
These sites are located adjacent to src homology region 2 ( SH 2 ) binding motifs ( YVPM motif : Y 447 , Y 472 , Y 619 ) specific for the phosphatidylinositol 3kinase ( PI3K ) . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The Src homology 2 containing inositol phosphatase SHIP 1 functions in hemopoietic cells to limit activation events mediated by PI3K products , including Akt activation and cell survival . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
We conclude that ME induced cardioprotection is mediated via Src dependent EGFR transactivation and activation of the PI3K and MAPK pathways . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
However , CIN 85 did not bind directly to the cytoplasmic domain of TNFR 1 ( TNFR 1 CYT ) but to Src family kinases , Cbl and the p85alpha subunit of phosphatidylinositol 3 kinase ( PI 3 K p85alpha ) . ^^^ Src bound directly to TNFR 1 CYT , but Cbl and PI 3 K p85alpha did not . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Our aim was to investigate the involvement of phosphatidylinositol 3 kinase ( PI3K ) , MEK 1 , and Src family tyrosine kinases in IGF 1 mediated oligodendrocyte progenitor survival . ^^^ These results suggest that 1 ) PI3K is essential for IGF 1 promoted cell survival , 2 ) downstream activation of Akt dependent and independent pathways is involved , and 3 ) Src like tyrosine kinases participate in IGF 1 induced Akt activation . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Several of the signaling molecules that are activated by growth factor receptors such as Src family kinases ( Src ) , phosphatidylinositol 3 ' kinase ( PI3K ) , phospholipase Cgamma ( PLCgamma ) , Ras , and SHP 2 were shown to mediate survival signals . ^^^ Deletion of the binding site for PI3K , but not for Src , RasGAP , SHP 2 , or PLCgamma , completely abolished the anti apoptotic effect . ^^^ Furthermore , the PDGF dependent anti apoptotic effect in non transfected cells was completely abolished by the PI3K inhibitor wortmannin , whereas inhibitors of Src , PLCgamma , ERK , or p 38 MAP kinase had no effect . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Pretreatment of cells with inhibitors of PI3K , Src family tyrosine kinases , and EGFR also decreased HUVEC migration . ^^^ In conclusion , these results suggest that Ang 2 mediates an increase in FAK and paxillin phosphorylation and induces HUVEC migration through signal transduction pathways dependent on PI3K and Src tyrosine kinase activation and EGFR transactivation . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
BRL 37344 treatment also increased choroidal endothelial cell invasion by 103 % above control values ; the invasion response was inhibited by PP 2 ( Src inhibitor ) , LY 294002 ( PI3K inhibitor ) , Akt inhibitor ( Akt 1 ) , and matrix metalloproteinase 2 / 9 inhibitor ( MMP 1 ) . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
We showed previously that flow activated the phosphatidylinositol 3 kinase ( PI3K ) , Akt , and endothelial nitric oxide synthase ( eNOS ) via Src kinase dependent transactivation of vascular endothelial growth factor receptor 2 ( VEGFR 2 ) . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Treatment with inhibitors of PI3K or of Syk , but not with those of MEK or Src family kinases , abolished the enhancement of FcgammaR mediated phagocytosis apparent in macrophages from SHPS 1 mutant mice . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
This study is the first demonstration that PLD 2 activation is implicated in Src dependent phosphorylation of Pyk 2 ( Tyr ( 580 ) and Tyr ( 881 ) ) by promoting the complex formation between Pyk 2 and activated Src in PC 12 cells exposed to H ( 2 ) O ( 2 ) , thereby resulting in activation of the survival signaling pathway PI3K / Akt / p70S6K . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Microglial proliferation was also inhibited by PP 2 ( Src inhibitor ) , LY 294002 ( PI3K inhibitor ) , and U 0126 ( MEK inhibitor ) . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
In conclusion , analyses of mAChR downstream effectors reveal that PKC zeta , PI3K , and Src family of tyrosine kinases , but not intracellular free Ca ( 2+ ) mobilization or conventional and novel PKC activation , are key molecules in the signal cascade leading to MAPK / ERK activation . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Src immunoprecipitates had associated phosphatidylinositol 3 kinase , or PI3K , activation in response to PDGF and thrombin but not EGF . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The growth factor mediated resensitization was dependent on an intact cytoskeleton and on the activation of protein phosphatases and of the phosphatidylinositol 3 kinase ( PI3K ) , but was independent of the activation of protein kinase C , src kinases , or extracellular signal regulated kinases . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
These analyses revealed an up regulation of Src tyrosine kinase and related signaling pathways [ phosphatidyl inositol 3 ' kinase ( PI3K ) / Akt , Janus activated kinase ( JAK ) 2 , signal transducer and activator of transcription ( STAT ) 3 , and extracellular signal regulated kinases ( ERK ) ] in both MTI / G Gly and hGAS mice compared with the wild type control animals as well as an overexpression of transforming growth factor alpha ( TGF alpha ) . ^^^ We report for the first time that the transition from a normal colonic epithelium to a hyperproliferative epithelium in MTI / G Gly and hGAS mice may be a consequence of the up regulation of Src , PI3K / Akt , JAK 2 , STAT 3 , ERKs , and TGF alpha . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The interactions between STAT 3 phosphorylation and p 38 , ERK1 / 2 , phosphatidylinositol 3 ( PI3K ) , mammalian target of rapamycin ( mTOR ) , Janus kinase ( JAK ) 2 and Src were evaluated by pretreating the cells with specific inhibitors including SB 202190 , PD 98059 , LY 294002 , wortmannin , rapamycin , AG 490 and PP 1 . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Suramin stimulated phosphorylation of Akt , a downstream kinase of phosphoinositide 3 kinase ( PI3K ) , extracellular signaling regulated kinase 1 / 2 ( ERK1 / 2 ) , and Src , but not the EGF receptor . ^^^ Furthermore , suramin induced outgrowth , scattering , and proliferation of RPTC are through Src mediated activation of the PI3K pathway but not ERK1 / 2 or the EGF receptor . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
RA induced activation of Rac 1 is mediated by phosphatidylinositol 3 kinase ( PI3K ) , probably because of phosphorylation of the p 85 regulatory subunit by Src kinases . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
In turn Src can activate PI3K and PKC delta , and all these signaling proteins are required for ODC induction . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Hyposmolarity also activated the non receptor tyrosine kinases , Src , focal adhesion kinase ( FAK ) , extracellular signal regulated protein kinase ( ERK ) 1 / 2 , and the tyrosine kinase target phosphatidyl inositol 3 kinase ( PI3K ) . ^^^ The hyposmotic induced activation of these kinases required the prior phosphorylation of ErbB 4 as shown by the effect of ErbB 4 blockade with AG 213 reducing by 85 95 % the phosphorylation of FAK and ERK1 / 2 , by 74 % and 36 % that of PI3K and Src , respectively . ^^^ The functional significance for cell volume regulation of the ErbB 4 Src PI3K signaling cascade is indicated by the 48 66 % decrease of the hyposmotic taurine efflux observed by inhibition of these kinases . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
However , the PI3K inhibitors do not show inhibitory effects on p 38 , Src , and EGFR . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The phosphatidylinositol 3 kinase ( PI3K ) selective inhibitor wortmannin , and mouse platelets deficient in Lyn , Src , Syk , Src homology 2 ( SH 2 ) domain containing leukocyte protein 76 ( SLP 76 ) , phospholipase Cgamma 2 ( PLCgamma 2 ) , linker for activation of T cells ( LAT ) , or Fc receptor gamma chain ( FcRgamma chain ) were used for these studies . ^^^ The results also clearly demonstrate that bt / VWF mediated agglutination induced TxA 2 production is dependent on signaling apparently initiated by Lyn , enhanced by Src , and propagated through Syk , SLP 76 , PI3K , PLCgamma 2 , and protein kinase C ( PKC ) . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
However , pharmacological inhibition of Src family PTK by 4 amino 5 ( 4 chlorophenyl ) 7 ( tert butyl ) pyrazolo [ 3 , 4 d ] pyrimidine ( PP 2 ) almost completely blocked H2O2 stimulated phosphorylation of the p 85 subunit of PI3K , ERK1 / 2 , and PKB . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Mechanistically , the activation of the PI3K / Akt pathway in keratinocyte differentiation depends on the activity of the epidermal growth factor receptor and Src families of tyrosine kinases and the engagement of E cadherin mediated adhesion . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Surprisingly , we found that Plexin B 1 stimulates PI3K Akt through the activation of an intracellular tyrosine kinase cascade that involves the sequential activation of PYK 2 and Src . ^^^ This results in the tyrosine phosphorylation of Plexin B 1 , the rapid recruitment of a multimeric signaling complex that includes PYK 2 , Src , and PI3K to Plexin B 1 and the activation of Akt . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
GDNF mediated effects require Src kinase and phosphatidylinositol 3 kinase ( PI3K ) / Akt activation . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Several agents interfering with intracellular targets that are components of key oncogenic signaling pathways , such as RAF kinase , phosphatidylinositol 3 kinase ( PI3K ) / Akt or Src , are in preclinical and early clinical development . `` Addictive ' ' targets , such as the Bcr Abl fusion protein in chronic myeloid leukemia ( CML ) , are critical for maintaining the malignant phenotype and hence represent an Achilles ' heel for selective drugs . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Both the PI3K / Akt and p 38 MAPK pathways are activated in a Src family kinase dependent fashion on EGF R activation and are important for EGF mediated VEGF production in pancreatic cancer cells . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Following M CSF treatment , FAK and the active forms of M CSFR and Src were redistributed to the cytoskeleton , where active ERK , JNK and PI3K were detectable . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
MG 132 induced DNA binding activity of C / EBPdelta , but not C / EBPbeta was regulated by p 38 , PI3K , Src , and protein kinase C . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Treatment of breast cancer cells and osteosarcoma cells with estradiol , estren , substance A and substance B led to non genomic activation of Akt ( protein kinase B ) and extracellular signal regulated kinase 1 / 2 ( ERK1 / 2 ) signaling cascades mediated by Src ( Rous Sarcoma Virus , non receptor tyrosine kinase ) and phosphatidylinositol 3 kinase ( PI3K ) stimulation . ^^^ As expected from PI3K and Src activation data , substances were as effective as estradiol in mediating vasorelaxation . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The morphological appearance of platelets produced through integrin alpha6beta1 activation is highly dependent on PI 3 kinase ( PI3K ) but less dependent on Src kinase . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Pull down assays with a fusion protein ( GST p85NC SH 2 ) , and coimmunoprecipitation studies , indicated that the insulin receptor substrate ( IRS ) , and not the epidermal growth factor and insulin like growth factor receptors or the Src tyrosine kinase , was physically associated with PI3K in these cells . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The anti apoptotic effect of Wnt3a was abrogated by inhibitors of canonical Wnt signaling , as well as by inhibitors of MEK , Src , phosphatidylinositol 3 kinase ( PI3K ) , or Akt kinases , or by the addition of cycloheximide to the culture medium . ^^^ However , Src , ERKs , PI3K , and Akt kinases were required for the anti apoptotic effects of Wnt5a . ^^^ These results demonstrate for the first time that Wnt proteins , irrespective of their ability to stimulate canonical Wnt signaling , prolong the survival of osteoblasts and uncommitted osteoblast progenitors via activation of the Src / ERK and PI3K / Akt signaling cascades . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
A critical step in this process is the phosphorylation of Tyr 397 of FAK , which creates a binding site for Src family kinases , PI3K ( phosphoinositide 3 kinase ) and Shc ( Src homology and collagen homology ) . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
L 59 neurite promoting activity was decreased in the presence of inhibitors of Src , Trk , PLCgamma , PKC , PI3K and MAPK . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Because 14 , 15 EET was found to be slightly more efficacious than 5 , 6 , 8 , 9 , and 11 , 12 EETs in stimulating HDMVEC tube formation and migration , we next focused on elucidation of the signaling mechanisms underlying its angiogenic activity . 14 , 15 EET stimulated Akt and S6K1 phosphorylation in Src and phosphatidylinositol 3 kinase ( PI3K ) dependent manner in HDMVECs . ^^^ Inhibition of Src and PI3K Akt mTOR signaling by both pharmacological and dominant negative mutant approaches suppressed 14 , 15 EET induced HDMVEC tube formation and migration in vitro and Matrigel plug angiogenesis in vivo . ^^^ In addition , 14 , 15 EET induced the expression of fibroblast growth factor 2 ( FGF 2 ) in Src and PI3K Akt dependent and mTOR independent manner in HDMVECs . ^^^ Together , these results show for the first time that Src and PI3K Akt signaling via targeting in parallel with FGF 2 expression and mTOR S6K1 activation plays an indispensable role in 14 , 15 EET induced angiogenesis . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Antisense oligodeoxynucleotides ( ODNs ) and inhibitors of Src , PI3K , p 38 , and NFkappaB significantly reduced rhMIF induced MN VCAM 1 and ICAM 1 expression ( P < . 05 ) . ^^^ Silencing RNA directed against MIF , and inhibitors of Src , PI3K , NFkappaB , anti VCAM 1 , and anti ICAM 1 significantly inhibited rhMIF induced adhesion of HL 60 cells to human dermal microvascular endothelial cells ( HMVECs ) or an endothelial cell line , HMEC 1 , in cell adhesion assays , suggesting the functional significance of MIF induced adhesion molecules ( P < . 05 ) . rhMIF also activated MN phospho Src , Akt , and NFkappaB in a time dependent manner . rhMIF induced VCAM 1 and ICAM 1 up regulation in 12 hours via Src , PI3K , and NFkappaB as shown by Western blotting and immunofluorescence . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Pure lipopolysaccharide or synthetic lipid A induces activation of p21Ras in primary macrophages through a pathway dependent on Src family kinases and PI3K . ^^^ LPS induced activation of p21Ras was inhibited in the presence of PP 2 , LY 294002 , or wortmannin , suggesting that it depends on the activity of one or more members of the Src kinase family and the subsequent activation of PI3K . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
In this study , we show that ligation of CD 28 by its natural ligand B 7 1 / CD80 , induces tyrosine phosphorylation of Gab 2 and its coassociation with Src homology phosphatase ( SHP ) 2 and class IA PI3K in Jurkat cells . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The E76K mutation in the N terminal Src homology 2 domain increased interactions of mutant SHP 2 with Grb 2 , Gab 2 , and p 85 , leading to hyperactivation of IL 3 induced Erk and phosphatidylinositol 3 kinase ( PI3K ) pathways . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Our data showed that extracellular signal regulated kinase ( ERK ) pathway inhibitor PD 98059 , but not the c Jun N terminal kinase ( JNK ) inhibitor SP 600125 , p 38 kinase inhibitor SB 203580 , and PI3K inhibitor wortmannin , attenuated Src induced MMP 2 promoter activity . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
In addition , gp 130 activation leads to both PI3K and Src activation . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
We show here that EGF R transactivation was sensitive to pertussis toxin ( PTX ) and phosphoinositide 3 kinase ( PI3K ) inhibitors and that it occurred independently from Src activity , despite the observation of a strong impairment of LTD 4 induced DNA synthesis following Src inhibition . ^^^ While PI3K and ROS involvement is an early event , the activation of Src occurs downstream of EGF R activation and is followed by the classical Ras ERK1 / 2 signaling pathway to control G 1 progression and cell proliferation . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Using a GST ( glutathione S transferase ) fusion protein containing the p 85 N terminal SH 2 ( Src homology 2 ) domain as ' bait ' followed by MS / MS ( tandem MS ) , we identified a 70 kDa fragment of the p 70 PDGFR beta ( platelet derived growth factor receptor beta ) as a signalling adapter that is phosphorylated and recruits the p 85 subunit of PI3K after Ang 2 stimulation of AT 1 ( Ang 2 subtype 1 ) receptors on VSMCs . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Inhibitors towards tyrosine kinases , such as genistein and PP 1 , or src specific SU 6656 , but not PI3K and mTor inhibitors , lead to a reduction in tyrosine phosphorylation of S6K . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Thus , G ( q / 11 ) coupled receptors are the principal GPCR subfamily mediating cooperative mitogenic signaling in ASM , acting through Gbetagamma dependent , and Src / arrestin independent activation of PI3K and p70S6K . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
The signaling that results in TxA 2 production was shown to be initiated by Lyn , enhanced by Src , and propagated through Syk , SLP 76 , PI3K , PLCgamma 2 , and PKC . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Phosphorylation of extracellular signal regulated kinase ( ERK ) , AKT ( a major substrate of phosphatidylinositol 3 ' kinase [ PI3K ] ) , Src at tyrosine Y 416 , and EGFR at Y 845 was analyzed by Western blotting with antibodies specific to phosphorylated proteins . ^^^ CONCLUSIONS : These results suggest that Src kinase mediates wound induced EGFR transactivation and participates in a pathway to activate the PI3K AKT pathway downstream of EGFR in HCECs . . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
Moreover , there have been data to support the involvement of three main signaling pathways that involve PKC , SRC , and PI3K kinases in the regulation of the head formation and in the expression of several head specific genes . ^^^
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
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Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA
Interacting proteins: P12931 and P27986	Pubmed	SVM Score :0.0
NA