Pubmed abstracts for Protein-Protein Interaction search result :


Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.58799893
We find that Gas 6 , a ligand for the Axl and Rse / Tyro3 receptor protein tyrosine kinase family , stimulates human Schwann cell growth , increasing both cell number and thymidine incorporation . 0.58799893^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.51160107
This mechanism is supported by our observation that GAS 6 binds to 32D parental cells which then permits their aggregation with untreated 32D Axl cells . 0.51160107^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.70987551
The Gas 6 protein has been shown to associate with plasma membrane phosphatidylserine by its amino terminal portion , while its carboxyl terminal portion can bind and activate Mer and its related RTKs , Axl and Tyro 3 . 0.70987551^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.62487883
One of the most interesting aspects of this hypothetical protein is that its Gla domain is highly homologous to the Gla domain of Gas 6 , a ligand for Axl , while its receptor tyrosine kinase domain is highly homologous to Axl . . 0.62487883^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.76129179
Axl has been described to act as a mitogenic factor along with its ligand Gas 6 . 0.76129179^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.86915351
The receptor tyrosine kinase Axl has been shown to be activated by its ligand Gas 6 and by oxidative stress in the form of hydrogen peroxide . 0.86915351^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.51967298
Soluble Axl is generated by ADAM 10 dependent cleavage and associates with Gas 6 in mouse serum . 0.51967298^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Ligands for Dtk and Ufo have been identified as protein S and the related molecule Gas 6 , respectively . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
The anticoagulation factor protein S and its relative , Gas 6 , are ligands for the Tyro 3 / Axl family of receptor tyrosine kinases . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Recently , we have identified an Axl ligand , GAS 6 . ^^^ Surprisingly , GAS 6 stimulated 32D Axl cells exhibited no blockage to apoptosis or mitogenic response which is correlated with the absence of Ras / ERK activation . ^^^ Furthermore , our data suggest that the GAS 6 Axl interaction does not induce mitogenesis and that its exact role remains to be determined . . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Characterization of Gas 6 , a member of the superfamily of G domain containing proteins , as a ligand for Rse and Axl . ^^^ The Gla domain and epidermal growth factor like repeats were not required for receptor binding , as deletion variants of Gas 6 which lacked these domains bound to the extracellular domains of both Rse and Axl . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Gas 6 , the ligand of Axl tyrosine kinase receptor , has mitogenic and survival activities for serum starved NIH3T3 fibroblasts . ^^^ Reversible growth arrest has been characterised for enhanced expression of a set of genes called gas ( growth arrest specific ) . gas 6 product ( Gas 6 ) is a secreted protein that was identified as the ligand for the tyrosine kinase receptor Axl . ^^^ This mitogenic activity of Gas 6 strictly correlates with its ability to interact with NIH3T3 endogenous Axl receptor since it can be abolished by soluble Axl extracellular domain and activates both Axl intrinsic kinase activity and the downstream MAPK pathway . ^^^ Moreover when ectopic Axl overexpression is performed by microinjection in serum starved NIH3T3 cells , addition of a non mitogenic level of Gas 6 induces selective entry into S phase in Axl overexpressing cells . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
The product of growth arrest specific gene 6 ( Gas 6 ) , structurally homologous to the anticoagulant protein S , was recently identified as the ligand for Axl and Sky , but the ligand for Mer remained unknown . ^^^ Co precipitation analysis , using soluble receptors of Axl , Sky , and Mer ( Axl Fc , Sky Fc , and Mer Fc ) composed of the extracellular domain of receptors fused to the Fc domain of immunoglobulin G 1 , clearly showed that Gas 6 , but not protein S , specifically bound to Axl Fc , Sky Fc , and Mer Fc fusion proteins . ^^^ Quantitative kinetic analyses using a BIAcore biosensor instrument revealed dissociation constants ( Kd ) of the binding of rat Gas 6 to Axl Fc , Sky Fc , and Mer Fc are 0 . 4 , 2 . 7 , and 29 nM , respectively . ^^^ We also found that Gas 6 stimulated tyrosine phosphorylation of Axl , Sky , and Mer receptors ectopically expressed in Chinese hamster ovary cells . ^^^ Taken together , these findings suggest that Gas 6 is a common ligand for Axl , Sky , and Mer , all known members of an Axl / Sky receptor subfamily . . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Gas 6 has previously been shown to activate both Axl and Rse / Tyro3 , two other receptor tyrosine kinases in the same family as Mer . ^^^ The apparent relative association and dissociation rate constants of Gas 6 for soluble Axl , Rse / Tyro3 and Mer were compared using surface plasmon resonance . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Protein S and a structurally similar protein , Gas 6 , have been found to stimulate members of the Axl / Sky family of receptor tyrosine kinases . ^^^ Human Gas 6 is able to activate Axl and Sky . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Requirement of phosphatidylinositol 3 kinase dependent pathway and Src for Gas 6 Axl mitogenic and survival activities in NIH 3T3 fibroblasts . ^^^ Gas 6 is a secreted protein previously identified as the ligand of the Axl receptor tyrosine kinase . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
OBJECTIVE : To determine if human articular chondrocytes express the axl tyrosine kinase receptor and its ligand Gas 6 , a protein product of growth arrest specific gene 6 , and to determine if Gas 6 and axl function in the regulation of chondrocyte growth and survival . ^^^ METHODS : The presence of Gas 6 and axl was examined in situ in human articular cartilage by immunohistochemistry and in vitro in cell culture studies using primary human chondrocytes and immortalized human chondrocytes . ^^^ The ability of recombinant Gas 6 to mediate adhesion of chondrocytes and to stimulate chondrocyte axl phosphorylation was determined . ^^^ Studies of the role of Gas 6 and axl in cell proliferation and survival were also performed . ^^^ RESULTS : Both Gas 6 and axl were detected in cartilage by immunohistochemical staining . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
The biological activity of the ligand for Axl , the product of growth arrest specific gene 6 ( Gas 6 ) , was then evaluated , demonstrating modest mitogenic activity in thyroid carcinoma cells overexpressing Axl . ^^^ Furthermore , Gas 6 is identified as a novel growth factor for thyroid carcinoma cells overexpressing Axl receptor tyrosine kinase . . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
GAS 6 induces Axl mediated chemotaxis of vascular smooth muscle cells . ^^^ GAS 6 stimulation induces Axl autophosphorylation in human vascular smooth muscle cells , indicating that specific GAS 6 Axl interactions may be associated with GAS 6 directed chemotaxis . ^^^ To test this hypothesis , vascular smooth muscle cells overexpressing Axl were generated by gene transfer and assessed for their ability to migrate along a GAS 6 gradient . ^^^ These Axl overexpressors exhibited 2 5 fold increased sensitivity to GAS 6 induced chemotaxis . ^^^ Furthermore , vascular smooth muscle cells expressing the kinase dead mutant of Axl or exposure to the soluble Axl extracellular domain showed attenuated GAS 6 induced migration . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
GAS 6 is a ligand for the tyrosine kinase receptors Rse , Axl , and Mer , but its function is poorly understood . ^^^ Previous studies reported that both GAS 6 and Axl are expressed by vascular endothelial cells ( EC ) , which play a key role in leukocyte extravasation into tissues during inflammation through adhesive interactions with these cells . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Northern blot analysis indicated increased mRNA expression for the secreted Axl ligand , Gas 6 , in injured carotids , with a time course paralleling that of Axl upregulation . ^^^ Axl and Gas 6 expression were temporally correlated with neointima formation , suggesting a role for Axl signaling in this process . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
The product of a gas 6 splice variant allows the release of the domain responsible for Axl tyrosine kinase receptor activation . ^^^ The product of gas 6 ( Gas 6 ) is a growth factor with high level of similarity to protein S and was identified as the ligand for Axl family of tyrosine kinase receptors . ^^^ Furthermore a deletion mutant of Gas 6 containing only the D domain was shown to similarly activate Axl receptor phosphorylation unequivocally demonstrating that D domain can act as a signalling molecule . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
GAS 6 , the ligand of Axl and Rse receptors , is expressed in hematopoietic tissue but lacks mitogenic activity . ^^^ GAS 6 , a gene previously identified as growth arrest specific , has been demonstrated to be the ligand of Axl , a novel tyrosine kinase receptor widely expressed in both normal and neoplastic hematopoietic tissue . ^^^ Despite the fact that both the Axl receptor and its ligand , GAS 6 , are expressed in hematopoietic tissue , the biological role of their interactions remains to be determined . . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
It has been also demonstrated that Gas 6 is a ligand of receptor tyrosine kinases Axl , Sky , and Mer . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Administration of the axl ligand , gas 6 , to peripheral transgenic blood samples eliminated excessive TNF alpha production in response to LPS stimulation . ^^^ As a means to better understand axl gas 6 biology , transgenic animals were produced which systemically expressed the gas 6 binding axl proteolytic cleavage product . ^^^ The observed phenotypes may be related to the axl receptor or proteolytic cleavage product competing with related axl family receptors for binding of the gas 6 ligand . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Axl gas 6 interaction counteracts E1A mediated cell growth suppression and proapoptotic activity . ^^^ The Axl ligand Gas 6 triggered a greater mitogenic effect in these ip 1 E1A Axl cells than in ip 1 E1A control cells and protected the Axl expressing cells from serum deprivation induced apoptosis . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
In mesangial cells , Gas 6 and its receptor Axl were expressed . ^^^ In addition , exogenous Gas 6 phosphorylated Axl , activated extracellular signal regulated kinase , and stimulated [ 3H ] thymidine incorporation in mouse mesangial cells . ^^^ Addition of the extracellular domain of Axl to the CM inhibited its mitogenic effect on mesangial cells , suggesting that this vitamin K dependent growth factor is Gas 6 . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Gene expression of Rse , Axl , Mer , and Gas 6 in the testis was studied by reverse transcriptase polymerase chain reaction ( RT PCR ) and Northern blot analysis . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
HMC 1 cells also expressed gas 6 , the putative ligand of axl , which has been shown to induce axl mediated homotypic binding . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Gas 6 ( growth arrest specific gene 6 ) is a ligand for members of the Axl subfamily of receptor protein tyrosine kinases . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Tyro 3 , Axl and Mer are all normally expressed by Sertoli cells during postnatal development , whereas their ligands , Gas 6 and protein S , are produced by Leydig cells before sexual maturity , and by both Leydig and Sertoli cells thereafter . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Expression of receptor tyrosine kinase Axl and its ligand Gas 6 in rheumatoid arthritis : evidence for a novel endothelial cell survival pathway . ^^^ Gas 6 ( for growth arrest specific gene 6 ) , which is a ligand for Axl and is related to the coagulation factor protein S , was found in synovial fluid and tissue from patients with RA and osteoarthritis . ^^^ Gas 6 bound to HUVECs ; soluble Axl inhibited this binding . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
The Axl protein is a member of a new family of receptor tyrosine kinases , of which the ligand , Gas 6 , a protein S related molecule , recently was proved to be a mitogenic factor for human thyroid cells . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Gas 6 was identified as the ligand for Axl tyrosine kinase receptor family . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Inhibition of Gas 6 by warfarin and the extracellular domain of its receptor , Axl , abolished phosphorylation of STAT 3 in vivo . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Gas 6 , a ligand of receptor tyrosine kinases Axl , Sky , and Mer , potentiates cell proliferation and prevents cell death . ^^^ In our previous study , we demonstrated that Gas 6 specifically binds to phosphatidylserine ( PS ) and links Axl expressing cells to the PS coated surface . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
GAS 6 is a ligand for the Axl ( Ufo / Ark ) , Sky ( Dtk / Tyro3 / Rse / Brt / Tif ) , and Mer ( Eyk ) family of tyrosine kinase receptors and binds to these receptors via tandem G domains at its C terminus . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
In this review , we consider the experimental evidence pointing to significant roles for the Axl receptor tyrosine kinase and its ligand , Gas 6 , in the vasculature . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Gas 6 is a growth factor related to protein S that was identified as the ligand for the Axl receptor tyrosine kinase ( RTK ) family . ^^^ We show that Axl RTK but not Rse is efficiently activated by Gas 6 in density inhibited C57MG cells . ^^^ These results suggest that Gas 6 Axl interaction , through stabilization of beta catenin , may have a role in mammary development and / or be involved in the progression of mammary tumors . . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Gas 6 regulates mesangial cell proliferation through Axl in experimental glomerulonephritis . ^^^ Previously , we demonstrated that the product of growth arrest specific gene 6 ( Gas 6 ) stimulates mesangial cell proliferation through binding to its cell surface receptor Axl in vitro . ^^^ In the present study , therefore , we examined in vivo roles of Gas 6 and Axl in an experimental model of mesangial proliferative glomerulonephritis induced by the injection of anti Thy1 . 1 antibody ( Thy 1 GN ) . ^^^ In Thy 1 GN , expression of Gas 6 and Axl was markedly increased in glomeruli , and paralleled the progression of mesangial cell proliferation . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Gas 6 promotes Axl mediated survival in pulmonary endothelial cells . ^^^ We examined Gas 6 Axl interactions in human pulmonary artery endothelial cells ( HPAEC ) and in Axl transduced HPAEC to test Gas 6 function during endothelial cell survival . ^^^ We identified the 5 . 0 kb Axl , 4 . 2 kb Rse , and 2 . 6 kb Gas 6 mRNAs in HPAEC . ^^^ In addition , the Axl receptor is constitutively phosphorylated in growth arrested cultures , and exogenous Gas 6 enhanced Axl phosphorylation threefold . ^^^ Transduction of a full length Axl cDNA into HPAEC resulted in 54 % fewer apoptosing cells after Gas 6 treatment . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Gas 6 is the ligand of Axl receptor tyrosine kinase ; upon binding to its receptor Gas 6 activates the phosphatidylinositol 3 OH kinase ( PI3K ) and its downstream targets S6K and Akt . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
The growth arrest specific gene 6 encodes a secreted protein , Gas 6 , which was originally identified as the ligand of a receptor , Axl , with tyrosine kinase activity . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
In this study , we have analysed the expression of the Axl protein and its ligand , Gas 6 , in human lung cancer cell lines of different histological origin . ^^^ Expression of the Axl ligand Gas 6 was detected in approximately 80 % of all cell lines investigated . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Akt is required for Axl Gas 6 signaling to protect cells from E1A mediated apoptosis . ^^^ We have previously identified that E1A suppresses the expression of Axl , a transforming tyrosine kinase and that Axl Gas 6 receptor ligand interaction prevents E1A transfectants from apoptosis induced by serum deprivation . ^^^ To determine how the Axl Gas 6 interaction prevents E1A mediated apoptosis , we analysed the expression of anti apoptotic molecules and found that the activated form of Akt was suppressed in the E1A transfectant ip 1 E1A and that Gas 6 was able to activate Akt in ip 1 E1A cells reexpressing Axl ( ip 1 E1A Axl ) . ^^^ Thus , we conclude that activated Akt is required for Axl Gas 6 signaling to prevent E1A mediated apoptosis induced by serum deprivation . ^^^ Downstream molecules of Akt , including NF kappaB , Fas ligand , and BAD were examined , among which phosphorylation of BAD by Axl Gas 6 signaling is associated with the anti apoptotic activity of Akt in our study . . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Therefore , we examined the gene expression of Gas 6 and its receptors Rse , Axl , and Mer in a rat model of CR . ^^^ The action of Gas 6 in rat kidney is mainly mediated through the Rse receptors rather than the Axl and Mer receptors . . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Identification of Gas 6 , a putative ligand for Sky and Axl receptor tyrosine kinases , as a novel neurotrophic factor for hippocampal neurons . ^^^ Gas 6 is a ligand for all members of the Axl family , each of which ( Axl , Sky , and c Mer ) has different affinities to Gas 6 . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
We demonstrated the expression of Gas 6 , the protein product of the growth arrest specific gene 6 ( gas 6 ) and a member of the vitamin K dependent protein family , and its receptor tyrosine kinases , Axl and Sky , in human uterine and ovarian endometriotic endometria using RT PCR Southern blot analysis and immunohistochemistry . ^^^ Gas 6 , Axl and Sky mRNA were detected in all samples analysed . ^^^ There was no significant difference between the levels of Sky mRNA in normal uterine and endometriotic endometria ; however , the levels of Gas 6 and Axl mRNA in endometriotic endometria were significantly higher than in normal endometria . ^^^ In the immunohistochemical study , Gas 6 , Axl and Sky were found in endometrial glandular cells and stromal cells in all samples analysed . ^^^ This study demonstrates the coexpression of receptor tyrosine kinases and their ligand , Gas 6 , in normal uterine and ovarian endometriotic endometria , and the overexpression of Axl and Gas 6 in endometriotic endometria . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Receptor tyrosine kinases of the Axl family are activated by Gas 6 , the product of growth arrest specific gene 6 . ^^^ Gas 6 Axl signaling is implicated in cell survival , adhesion , and migration . ^^^ Mutagenesis of some residues in this patch reduces Gas 6 LG binding to the extracellular domain of Axl as well as Axl activation in glioblastoma cells , identifying a component of the receptor binding site of Gas6 . . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Axl ligand , the survival factor growth arrest specific gene 6 product ( Gas 6 ) , was released into the conditioned medium , and by Western blot analysis , similar amounts of protein were found at pH 7 . 0 and 7 . 4 . ^^^ Furthermore , overexpression of either soluble Axl or antisense Gas 6 mRNA partially reverted the protective effect of acidification , increasing approximately 2 . 5 fold the number of apoptotic cells at pH 7 . 0 ( control 19 . 3+ / 2 . 7 % , soluble Axl 48 . 9+ / 9 . 7 % , P < 0 . 001 ; antisense Gas 6 49 . 3+ / 14 . 3 % , P < 0 . 03 ) . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Axl receptor tyrosine kinase is implicated in several malignancies and is the receptor for the vitamin K dependent growth factor Gas 6 . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Expression of receptor type tyrosine kinase , Axl , and its ligand , Gas 6 , in pediatric thyroid carcinomas around chernobyl . ^^^ The Axl protein is a member of a new family of receptor tyrosine kinases , which the ligand , Gas 6 , a protein S related molecule , has recently been identified . ^^^ We previously clarified the expression of Axl and mitogenic action of Gas 6 in thyroid carcinoma cells . ^^^ To investigate the involvement of Gas 6 Axl signaling in pediatric thyroid carcinoma further , we examined tissues obtained from 17 patients with thyroid papillary carcinomas from Gomel , Belarus , by immunohistochemistry and in situ hybridization . ^^^ Axl and Gas 6 were overexpressed in 76 . 5 % and 70 . 6 % of cases , respectively . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
We have reported that Gas 6 ( growth arrest specific gene 6 ) and its receptor , Axl , play a key role in the development of glomerulonephritis . ^^^ The glomerular expression of Gas 6 and Axl was increased in those rats . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Western blot analysis demonstrated that confluent pericytes also secrete the Axl ligand , Gas 6 . ^^^ Immunoprecipitation of confluent cell lysates with an anti phosphotyrosine antibody followed by Western blotting using an anti Axl antibody , demonstrated that Axl was active in confluent pericytes and that its activity could not be further enhanced by incubating the cells with recombinant Gas 6 . ^^^ The addition of recombinant Axl extracellular domain ( ECD ) to pericyte cultures inhibited the phosphorylation of Axl by endogenous Gas 6 and enhanced the rate of nodule mineralization . ^^^ These effects were inhibited by coincubation of pericytes with Axl ECD and recombinant Gas 6 . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
In humans the sole known ligand for the Axl / Rse / Mer kinases is growth arrest specific gene 6 ( Gas 6 ) , which in the CNS is secreted by neurons and endothelial cells . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Growth arrest specific gene 6 ( Gas 6 ) and its receptors Rse , Axl and Mer have recently been found to be involved in a rat model of chronic allograft nephropathy ( CAN ) . ^^^ Gas 6 receptors were not upregulated in any of the allograft groups , except for the Axl receptor , which increased only in acute tubular necrosis ( P < 0 . 01 ) . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
BACKGROUND : Gas 6 , the protein product of the growth arrest specific gene 6 ( gas 6 ) , a member of the vitamin K dependent protein family , was identified as a ligand for the Axl / Sky family of receptor tyrosine kinases . ^^^ The aim of the present study was to test for the presence of Gas 6 and its receptors Axl and Sky , related to specific growth in uterine endometrial cancers , and to evaluate their plausible growth potential and mechanism . ^^^ In uterine endometrial cancers , the mRNA levels and histoscores of Gas 6 , Axl and Sky were determined by competitive RT PCR using recombinant RNA and immunohistochemical studies , respectively . ^^^ RESULTS : The mRNA levels and the histoscores of Gas 6 and Axl in well differentiated endometrial cancers ( G 1 EC ) were significantly higher than in normal uterine endometrium ( NE ) and in moderately and poorly differentiated endometrial cancers ( G 2 + G 3 EC ) . ^^^ CONCLUSIONS : Gas 6 and Axl signal transduction is aberrantly stimulated in well differentiated endometrial cancers , plausibly related to tumor progression due to protection from apoptosis in cancers cells . . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
The expression of Gas 6 , the protein product of the growth arrest specific gene 6 ( gas 6 ) , a member of the vitamin K dependent protein family , and the receptor tyrosine kinases Axl and Sky and their mRNAs in uterine leiomyoma and normal uterine myometrium tissues were investigated by competitive RT PCR Southern blot analysis using recombinant RNA and immuno histochemical analysis respectively . ^^^ There was no significant difference between the histoscores and levels of Sky mRNA in uterine leiomyoma and normal uterine myometrium , although the levels of Gas 6 and Axl mRNAs in uterine leiomyoma were significantly higher than in normal uterine myometrium in each case . ^^^ It is suggested that Gas 6 and Axl signal transduction is aberrantly stimulated in uterine leiomyoma , possibly related to its growth . . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Axl is a receptor tyrosine kinase that is activated by Gas 6 , a growth factor that belongs to the vitamin K dependent protein family . ^^^ Although Gas 6 binding to Axl has been shown to transmit mitogenic and / or antiapoptotic signals to a variety of cell types , the role of the Axl Gas 6 system in normal and pathological lens biology is not known . ^^^ We demonstrate for the first time that Axl protein is expressed in normal rat and bovine lens and that its ligand , Gas 6 , is present in bovine aqueous humor . ^^^ We further show that human recombinant Gas 6 is able to act as a growth factor in cultured human lens epithelial cells by activating Axl and then the AKT signaling pathway . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Axl has been shown to mediate cell growth and survival through its ligand Gas 6 in non transformed cells . ^^^ To test whether stimulation of Axl can enhance survival of uveal melanoma cells , we assessed the degree of mitogenesis and cell survival by bromodeoxyuridine incorporation and trypan blue exclusion , respectively , upon stimulation of Mel 290 uveal melanoma cells with Gas 6 in vitro . ^^^ We further demonstrate that these effects occur specifically through the Axl receptor by modulating the expression of Axl with an antisense construct . cDNA microarray analysis of 12 , 687 genes then revealed that Gas 6 stimulation of Axl in Mel 290 cells results primarily in the down regulation of Cyr 61 , a member of the CCN protein family involved in tumor progression . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
BACKGROUND : Growth arrest specific gene 6 ( Gas 6 ) and its binding partner , the receptor tyrosine kinase Axl , are important mediators in experimental nephritis . ^^^ RESULTS : Gas 6 and Axl immunofluorescence was barely detectable in normal kidney . ^^^ Gas 6 and Axl upregulation was a prominent but nonspecific finding in these renal diseases . ^^^ Confocal microscopy and Western blot showed Ang 2 dependent Gas 6 and Axl expression . ^^^ An antisense probe against the p 22 phox unit of NADPH oxidase suppressed Ang 2 induced Gas 6 and Axl expression . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
The product of the growth arrest specific gene 6 ( GAS 6 ) , a ligand for the Axl , Sky , and Mer tyrosine kinase receptors , is a vitamin K dependent protein , structurally related to anticoagulant protein S . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Hydrogen peroxide activates the Gas 6 Axl pathway in vascular smooth muscle cells . ^^^ Axl phosphorylation was partly dependent on production of its endogenous ligand , growth arrest gene 6 ( Gas 6 ) , because Axl Fc , a fragment of Axl extracellular domain that neutralizes Gas 6 , inhibited H ( 2 ) O ( 2 ) induced Axl phosphorylation by 50 % . ^^^ Axl phosphorylation by H ( 2 ) O ( 2 ) was also attenuated by warfarin , which inhibits Gas 6 activity by preventing post translational modification . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Intracellular signaling pathways involved in Gas 6 Axl mediated survival of endothelial cells . ^^^ Gas 6 is a gamma carboxylated ligand for the receptor tyrosine kinase Axl . ^^^ Gas 6 Axl interactions can rescue endothelial cells from apoptosis , and this study examined the intracellular signaling mechanisms responsible for this phenomenon . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
The protein product of growth arrest specific gene 6 ( Gas 6 ) , is the biological ligand for the Axl subfamily of receptor tyrosine kinases . ^^^ Gas 6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase . ^^^ The mitogenic effects of Gas 6 were inhibited by neutralising anti Gas 6 antibodies and by a soluble Axl ectodomain fusion protein . ^^^ In contrast , recombinant Gas 6 from cells treated with warfarin , which prevents the gamma carboxylation reaction , neither stimulated fibroblast proliferation nor activated Axl tyrosine phosphorylation . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
A recent series of studies has revealed the in vivo roles of Gas 6 and its receptor Axl in the progression of various kidney diseases . ^^^ RECENT FINDINGS : The expression of Gas 6 and Axl is upregulated in an acute model of glomerulonephritis in rats , and the interference of the Gas6 / Axl pathway by warfarin or the extracellular domain of Axl inhibits the progression of diseases . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Gas 6 inhibits apoptosis in vascular smooth muscle : role of Axl kinase and Akt . ^^^ Treatment of VSMC with 100 ng / ml Gas 6 ( the putative ligand for Axl ) decreased apoptosis to 8 . 9 + / 0 . 7 % ( P = 0 . 002 , N = 17 ) as compared to a decrease with 10 % serum to 3 . 0 + / 0 . 2 % ( P = 0 . 001 , N = 17 ) . ^^^ The ability of Gas 6 to prevent apoptosis required both Gas 6 binding to Axl and Axl kinase activity since treatment with a soluble , competitive Axl extracellular domain protein or transfection of a kinase inactive mutant ( Axl K567R ) completely prevented the anti apoptotic effect . ^^^ Prevention of apoptosis by Gas 6 Axl required activation of phosphatidyl inositol 3 kinase ( PI3K ) as shown by treatment with LY 294002 or transfection of an Axl deletion mutant that does not bind PI3K ( Axl triangle up PI3K ) . ^^^ There was no significant role for ERK1 / 2 in the anti apoptotic effects of Gas 6 Axl since ERK1 / 2 activity was maintained in cells transfected with Axl triangle up PI3K and Axl K567R . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
OBJECTIVES : Gas 6 , the protein product of the growth arrest specific gene 6 ( gas 6 ) , a member of the vitamin K dependent protein family , was identified as a ligand for the Axl / Sky family of receptor tyrosine kinases . ^^^ The aim is to study for the presence of Gas 6 and its receptor Axl and Sky related to specific growth in the ovarian cancers , and to evaluate their plausible growth potential and mechanism . ^^^ METHODS : In ovarian cancers of 90 cases , the histoscores and mRNA levels of Gas 6 , Axl and Sky were determined by immunohistochemistry and competitive reverse transcription polymerase chain reaction Southern blot analysis using the recombinant RNA , respectively . ^^^ RESULTS : The histoscores and mRNA levels of Gas 6 and Axl in ovarian cancers were significantly higher than in normal ovaries , regardless of histopathological type or clinical stage of ovarian cancers . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
The AXL / UFO family of tyrosine kinases is characterized by a common N CAM ( neural adhesion molecule ) related extracellular domain and a common ligand , GAS 6 ( growth arrest specific protein 6 ) . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
GAS 6 , the product of a growth arrest specific ( GAS ) gene , is the ligand of the tyrosine kinase receptor Axl . ^^^ GAS 6 and Axl are both expressed in endothelial cells , where they are involved in many processes such as leukocyte transmigration through capillaries and neointima formation in injured vessels . ^^^ Here , we show that Axl stimulation by GAS 6 results in inhibition of the ligand dependent activation of vascular endothelial growth factor ( VEGF ) receptor 2 and the consequent activation of an angiogenic program in vascular endothelial cells . ^^^ GAS 6 activates the tyrosine phosphatase SHP 2 ( SH 2 domain containing tyrosine phosphatase 2 ) , which is instrumental in the negative feedback exerted by Axl on VEGF A activities . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Gas 6 ( growth arrest specific gene 6 ) is a vitamin K dependent protein known to activate the Axl family of receptor tyrosine kinases . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Gas 6 induces proliferation in prostate carcinoma cell lines expressing the Axl receptor . ^^^ The ligand of Axl , Gas 6 , is a 75 KDa multimodular protein with an N terminal gamma carboxy glutamic acid that is essential for binding . ^^^ Our results suggest that Axl overexpression and activation by Gas 6 could be involved in progression of prostate neoplastic disease . . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
A recent series of studies has revealed the in vivo roles of Gas 6 and its receptor Axl in the progression of acute and chronic glomerulonephritis , diabetic nephropathy , chronic allograft rejection , and human kidney diseases . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Here , we report that loss of any 1 of the Gas 6 receptors ( Gas 6 Rs ) , i . e . , Tyro 3 , Axl , or Mer , or delivery of a soluble extracellular domain of Axl that traps Gas 6 protects mice against life threatening thrombosis . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Gas 6 is a ligand for the Axl , C Mer , and Sky family of tyrosine kinase receptors . ^^^ METHODS AND RESULTS : Whereas Gas 6 , C Mer , and Sky were expressed in mature murine adipocytes , the expression of Axl was restricted to the stromal vascular fraction , which includes pre adipocytes . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Gas 6 receptors Axl , Sky and Mer enhance platelet activation and regulate thrombotic responses . ^^^ The current study evaluated the contribution of each of the three known Gas 6 receptors ( Axl , Sky and Mer ) in human and mouse platelet function . ^^^ In contrast , a stimulatory anti Axl antibody increased activation responses to these agonists , suggesting a potentiating role for Gas 6 in platelet activation . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Immunoexpression of Tyro 3 family receptors Tyro 3 , Axl , and Mer and their ligand Gas 6 in postnatal developing mouse testis . ^^^ In this study , we examined the localizations of Tyro 3 , Axl , Mer , and their ligand Gas 6 in postnatal mouse testes by immunohistochemistry . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Axl belongs to a particular subfamily of transmembrane receptor tyrosine kinases , the biological ligand for which is the growth / survival factor Gas 6 . ^^^ Stimulation of COS cells with Gas 6 caused increased Axl tyrosine phosphorylation although appeared not to influence the RanBPM Axl association . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Expression and role of Gas 6 protein and of its receptor Axl in hepatic regeneration from oval cells in the rat . ^^^ BACKGROUND & AIMS : The growth arrest specific gene 6 ( Gas 6 ) protein is a vitamin K dependent protein that binds to the Axl subfamily of tyrosine kinase receptors and exerts antiapoptotic and proliferative effects . ^^^ Because Gas 6 plays a role in development and tissue remodelling , we studied its expression as well as that of its high affinity receptor Axl in a well characterized model of hepatic regeneration from precursor oval cells . ^^^ WB F 344 cells , a hepatocytic precursor cell line , also expressed Gas 6 and Axl . ^^^ CONCLUSIONS : Our data demonstrate an expression of Gas 6 and of its receptor Axl by oval cells during hepatic regeneration . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Most strikingly , IL 15 treatment mimics stimulation by the Axl ligand , Gas 6 , resulting in a rapid tyrosine phosphorylation of both Axl and IL 15Ralpha , and activation of the phosphatidylinositol 3 kinase / Akt pathway . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Gas 6 is a novel member of the vitamin K dependent family of gamma carboxylated proteins and is a ligand for the receptor tyrosine kinase Axl . ^^^ Gas 6 Axl interactions have been shown to mediate cell survival in vascular endothelium . ^^^ Furthermore , the role of gamma carboxylation in gas 6 ' s survival effect on endothelium is demonstrated directly in that only carboxylated , but not decarboxylated , gas 6 protects endothelial cells from serum starvation induced apoptosis . gamma carboxylation is also required for both Axl phosphorylation and PI 3 kinase activation . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Structural basis for Gas 6 Axl signalling . ^^^ Receptor tyrosine kinases of the Axl family are activated by the vitamin K dependent protein Gas 6 . ^^^ The crystal structure at 3 . 3 A resolution of a minimal human Gas6 / Axl complex reveals an assembly of 2 : 2 stoichiometry , in which the two immunoglobulin like domains of the Axl ectodomain are crosslinked by the first laminin G like domain of Gas 6 , with no direct Axl / Axl or Gas6 / Gas6 contacts . ^^^ Gas 6 mediated Axl dimerisation is likely to occur in two steps , with a high affinity 1 : 1 Gas6 / Axl complex forming first . ^^^ Only the minor Gas 6 binding site is highly conserved in the other Axl family receptors , Sky / Tyro3 and Mer . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Growth arrest specific protein 6 ( gas 6 ) activity is mediated through the receptor tyrosine kinase family members Axl , Rse , and Mer , all of which are expressed in human oligodendrocytes . ^^^ The gas 6 protective effect was abrogated by the Axl decoy receptor Axl Fc , by the phosphatidylinositol 3 ( PI 3 ) kinase inhibitor LY 294002 [ 2 ( 4 morpholinyl ) 8 phenyl 1 ( 4H ) benzopyran 4 one ] , and in Akt 1 ( / ) oligodendrocytes . ^^^ We conclude that gas 6 signaling through the Axl receptor and the PI 3 kinase / Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha mediated cell death . . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
The protein product of the growth arrest specific gene 6 ( Gas 6 ) is a secreted ligand for tyrosine kinase receptors , among which Axl is the most widely distributed and displays the highest affinity for Gas 6 . ^^^ We investigated the expression and the role of Gas 6 and its receptor Axl in liver repair . ^^^ Axl , the high affinity receptor for Gas 6 , was detected in macrophages , HSC , and HSC / MFB . ^^^ In vitro , expression of gamma carboxylated Gas 6 was strongly induced in HSC along with their transformation into myofibroblasts , and it exerted an anti apoptotic effect on both HSC and HSC / MFB mediated by the Axl / PI3 kinase / Akt pathway . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Twist expression was activated by the Axl ligand Gas 6 and by protein S and apoptotic cells . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Statins protect human aortic smooth muscle cells from inorganic phosphate induced calcification by restoring Gas 6 Axl survival pathway . ^^^ In this study , we investigated the effect of statins on VSMC calcification by testing their effect on apoptosis , focusing in particular on regulation of the survival pathway mediated by growth arrest specific gene 6 ( Gas 6 ) , a member of the vitamin K dependent protein family , and its receptor , Axl . ^^^ Suppression of Gas 6 using small interfering RNA and the Axl extracellular domain abolished the preventive effect of statins on Pi induced apoptosis and calcification . ^^^ These data demonstrate that statins protected HASMC from Pi induced calcification by inhibiting apoptosis via restoration of the Gas 6 Axl pathway . . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
To determine whether Gas 6 amplifies the response to known platelet agonists through one or more of its receptor tyrosine kinases of the Tyro 3 family , mice deficient in any one of the Gas 6 receptors ( Gas 6 Rs : Tyro 3 , Axl , or Mer ) were submitted to thrombosis challenge and their platelet function . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
We demonstrate that Axl and its ligand Gas 6 are overexpressed in human glioma cell lines and that Axl is activated under baseline conditions . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
Axl , a receptor tyrosine kinase , whose ligand is Gas 6 , is highly induced in VSMC after carotid injury . ^^^ As expected , p Akt was decreased in Axl ( / ) , whereas there was no difference in Gas 6 expression . ^^^
Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
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Interacting proteins: Q14393 and P30530 Pubmed SVM Score :0.0
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