Pubmed abstracts for Protein-Protein Interaction search result :


Interacting proteins: P42768 and P60953 Pubmed SVM Score :1.0671759
Neural Wiskott Aldrich syndrome protein ( N WASP ) , a ubiquitously expressed WASP homologous protein , directly binds with Cdc 42 , activating Arp2 / 3 complex . 1.0671759^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.64921743
Contractile stimulation increased the association of neuronal Wiskott Aldrich syndrome protein with Cdc 42 and the Arp2 / 3 ( actin related protein ) complex in smooth muscle tissues expressing wild type Cdc 42 . 0.64921743^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.85550391
The gene responsible for Wiskott Aldrich syndrome , a disease affecting platelets and lymphocytes , has been cloned and its protein product ( WASp ) found to interact with the GTPase Cdc 42 . 0.85550391^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.79210093
N WASP induces extremely long actin microspikes only when co expressed with active Cdc 42 , whereas WASP , which is expressed in haematopoietic cells , does not , despite the structural similarities between WASP and N WASP . 0.79210093^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.51328659
Finally , we obtained the quite unexpected result that a WASP mutant deficient in binding to Cdc 42 still induced actin cluster formation , indicating that direct interaction between Cdc 42 and WASP is not required for the regulation of actin cytoskeleton . 0.51328659^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.76673248
The interactions between WASp , the Rho family GTPase Cdc 42 , and the cytoskeletal organising complex Arp2 / 3 are probably critical to many of these functions , which , when disturbed , translate into measurable defects of cell polarisation and motility . . 0.76673248^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.60304482
In contrast , the direct interaction of N WASP with the Rho GTPase Cdc 42 was not required for reconstitution of vesicle motility . 0.60304482^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.77600924
WASP binds directly to Cdc 42 through its GTPase binding domain ( GBD ) , but SCAR does not contain a GBD , and no direct binding has been found . 0.77600924^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.98625979
It was also found that different mutant WAS proteins from three affected males retained their ability to interact with Cdc 42 and that the level of expression of the WAS protein in these mutants was only 2 5 % of normal . 0.98625979^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.59200686
This TAT CRIB protein was shown to bind specifically to Cdc 42 GTP and to inhibit the chemotactic response of a T cell line to SDF 1 . 0.59200686^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Wiskott Aldrich syndrome protein , a novel effector for the GTPase CDC42Hs , is implicated in actin polymerization . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Two molecules were isolated , the Wiskott Aldrich syndrome protein ( WASP , a putative CDC 42 effector ) and a serine / threonine protein kinase ( PRK 2 , closely related to the putative Rho effector PKN ) . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
The affinity of the Cdc 42 binding domains of the CRIB motif of Wiskott Aldrich Syndrome protein and p 21 ( cdc42 / rac ) activated kinase 1 , and the RasGAP related domain of IQGAP 1 , which all inhibit the intrinsic rate of GTP hydrolysis of Cdc 42 , are found to be 4 , 0 . 7 , and 0 . 08 microM , respectively . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Here , we show that neural Wiskott Aldrich syndrome protein ( N WASP ) , which is a critical target for filopodium formation downstream of Cdc 42 , is required for assembly of the actin tail generated by intracellular S . flexneri . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
The Cdc42 / Rac interactive binding region motif of the Wiskott Aldrich syndrome protein ( WASP ) is necessary but not sufficient for tight binding to Cdc 42 and structure formation . ^^^ The binding of Cdc 42 induces a structural rearrangement of residues in the GBD / CRIB motif , or alternatively , the Wiskott Aldrich syndrome protein fragments have an ensemble of conformations , one of which is stabilized by Cdc 42 binding . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Tyrosine phosphorylation of the Wiskott Aldrich syndrome protein by Lyn and Btk is regulated by CDC 42 . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
One such effector , the Wiskott Aldrich syndrome protein ( WASP ) , is postulated to link activation of Cdc 42 directly to the rearrangement of actin . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Cdc 42 interacting protein 4 mediates binding of the Wiskott Aldrich syndrome protein to microtubules . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
The Rho family GTPase , Cdc 42 , can regulate the actin cytoskeleton through activation of Wiskott Aldrich syndrome protein ( WASP ) family members . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Neural Wiskott Aldrich syndrome protein ( N WASP ) is an actin regulating protein that induces filopodium formation downstream of Cdc 42 . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
The VirG protein expressed at one pole of the bacterium can recruit neural Wiskott Aldrich syndrome protein ( N WASP ) , a downstream effector of Cdc 42 . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
To further examine the role of Cdc 42 in E cadherin mediated cell cell adhesion , we developed an assay for active Cdc 42 using the GTPase binding domain of the Wiskott Aldrich syndrome protein . ^^^ By fusing the Wiskott Aldrich syndrome protein / GTPase binding domain to a green fluorescent protein , activation of endogenous Cdc 42 by E cadherin was demonstrated in live cells . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Whereas Cdc 42 must activate Wiskott Aldrich Syndrome protein ( WASP ) to stimulate nucleation by the Arp2 / 3 complex , VCA ( verpolin homology , cofilin , and acidic domain contained in the COOH terminal fragment of N WASP ) constitutively activates the Arp2 / 3 complex . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Neuronal Wiskott Aldrich Syndrome protein ( N WASP ) transmits signals from Cdc 42 to the nucleation of actin filaments by Arp2 / 3 complex . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Formation of podosomes has been shown to be dependent on the small GTPase CDC42Hs and its effector Wiskott Aldrich syndrome protein ( WASp ) . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Cdc 42 , Rac 1 , and the Wiskott Aldrich syndrome protein are involved in the cytoskeletal regulation of B lymphocytes . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Type 2 cells had morphology similar to that of cells transfected with neural Wiskott Aldrich Syndrome Protein ( N WASP ) , one of the established downstream effector molecules of Cdc 42 . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Here , we investigated the role of the actin regulator Wiskott Aldrich syndrome protein ( WASp ) , its effector the Arp2 / 3 complex and the Rho GTPases CDC42Hs , Rac and Rho in invasin / beta1 integrin triggered phagocytosis . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
The Cdc 42 GTPase , a member of the Rho subfamily of Ras proteins , can signal to the cytoskeleton through its effector , the Wiskott Aldrich syndrome protein ( WASP ) , activation of which results in localized polymerization of new actin filaments . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Previously we have shown that TCR endocytosis is regulated by the Wiskott Aldrich Syndrome protein ( WASp ) , a cytosolic effector which , upon interaction with the cdc 42 Rho GTPase , couples TCR engagement to Arp 2 / 3 complex mediated actin polymerization . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Phosphoinositide 3 kinase ( PI3K ) , small Rho GTPases , such as Cdc 42 and Rac 1 , and neuronal Wiskott Aldrich syndrome protein ( N WASP ) are key effectors that regulate dynamic changes in the actin cytoskeleton and cell migration . uPA and EGF stimulated chemotaxis , cytoskeletal rearrangements and activation of Cdc 42 , Rac 1 and N WASP were studied in the highly metastatic human breast cancer cell line MDA MB 231 . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
These results are consistent with Cdc 42 being critically involved in initiating the early events in phagocytosis by its ability to activate Pak and the Wiskott Aldrich Syndrome protein that triggers the localized polymerization of actin . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
The Rho protein Cdc 42 induces a significant conformational change in its downstream effector , the Wiskott Aldrich syndrome protein ( WASP ) . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
We show that the endocytic protein , dynamin , competes for binding to the SH 3 domains with the neural Wiskott Aldrich Syndrome protein , an actin filament nucleation protein that is a substrate for activated Cdc 42 . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
We have shown that WIP interacts with members of the Wiskott Aldrich syndrome protein family and is essential for filopodium formation regulated by Cdc 42 GTPase . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
The Wiskott Aldrich syndrome protein ( WASP ) is an effector of the Rho family GTPase Cdc 42 , whose activation leads to stimulation of the actin nucleating assembly , Arp2 / 3 complex . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
We have shown previously that Wiskott Aldrich syndrome protein ( WASP ) activation at the site of T cell APC interaction is a two step process , with recruitment dependent on the proline rich domain and activation dependent on binding of Cdc 42 GTP to the GTPase binding domain . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
We showed previously that binding to antigen presenting cells ( APCs ) induces localized activation of Cdc 42 and Wiskott Aldrich Syndrome protein ( WASP ) at the immune synapse . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Expression of the constitutively active Cdc 42 ( L 61 ) mutant increases the secretory response , recruits neural Wiskott Aldrich syndrome protein ( N WASP ) , and enhances actin polymerization in the subplasmalemmal region . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Involvement of the Wiskott Aldrich syndrome protein ( WASp ) in promoting cell activation requires its release from autoinhibitory structural constraints and has been attributed to WASp association with activated cdc 42 . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
PtdIns ( 4 , 5 ) P ( 2 ) rich lipid rafts can assemble into patches in a process depending on PtdIns ( 4 , 5 ) P ( 2 ) , Cdc 42 ( cell division control 42 ) , N WASP ( neural Wiskott Aldrich syndrome protein ) and actin cytoskeleton dynamics . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
We show that netrin 1 induced growth cone expansion requires Cdc 42 ( cell division cycle 42 ) , Rac 1 ( Ras related C 3 botulinum toxin substrate 1 ) , Pak 1 ( p 21 activated kinase ) , and N WASP ( neuronal Wiskott Aldrich syndrome protein ) and that the application of netrin 1 rapidly activates Cdc 42 , Rac 1 , and Pak 1 . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
The nucleotide switch in Cdc 42 modulates coupling between the GTPase binding and allosteric equilibria of Wiskott Aldrich syndrome protein . ^^^ We have developed a quantitative model of allosteric regulation of the Wiskott Aldrich syndrome protein ( WASP ) by the Rho GTPase Cdc 42 to better understand how GTPase binding is coupled to effector activation . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
In tracheal smooth muscle , agonist induced actin polymerization is mediated by activation of neuronal Wiskott Aldrich syndrome protein ( N WASp ) and the Arp ( actin related protein ) 2 / 3 complex , and activation of the small GTPase Cdc 42 regulates the activation of N WASp . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
We hypothesize that branching occurs when Arp2 / 3 is bound to Wiskott Aldrich syndrome protein ( WASP ) , which is in turn bound to Cdc 42 signaling complex ; Arp2 / 3 binding geometry is restricted by the membrane bound complex . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
In this study , we demonstrated that ACK 1 phosphorylates the Wiskott Aldrich syndrome protein ( WASP ) , a Cdc 42 effector that plays an important role in the formation of new actin filaments . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
We present examples for quantitative characterization of ( 1 ) Rac 1 10 GDP interaction , ( 2 ) Cdc 42 interaction with the GTPase binding domain of the Wiskott Aldrich syndrome protein ( three alternative approaches ) , ( 3 ) accelerated nucleotide exchange reaction of RhoA by the catalytic domains of p190RhoGEF , and ( 4 ) intrinsic and stimulated GTP hydrolysis reaction by the catalytic domain of p50RhoGAP . . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
The Wiskott Aldrich syndrome protein ( WASP ) and its homolog neuronal WASP ( N WASP ) are effectors of the Rho GTPase Cdc 42 and provide a direct link between activated membrane receptors and the actin cytoskeleton . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
The Wiskott Aldrich syndrome protein ( WASP ) is an effector of the Rho GTPase Cdc 42 and a key component of signaling pathways that regulate the actin cytoskeleton . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
RESULTS : A yeast two hybrid screen for proteins interacting with the human Cdc 42 GTPase identified WASP , a protein implicated in the immunodeficiency disorder Wiskott Aldrich syndrome ( WAS ) . ^^^ Recombinant WASP , expressed in Escherichia coli , also bound to Cdc 42 and weakly to Rac , but not at all to Rho . ^^^ The Cdc42 / Rac binding domain was identified in a region between amino acids 201 321 of WASP , and binding was dependent on Cdc 42 and Rac being in the GTP bound conformation . ^^^ Furthermore , WASP did not catalyze GTPase activation or nucleotide exchange activity on Cdc 42 . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
WIP binds to WASP at a site distinct from the Cdc 42 binding site and has actin as well as profilin binding motifs . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
RhoG dependent events are not mediated through a direct interaction with Rac 1 and Cdc42Hs targets such as PAK 1 , POR 1 , or WASP proteins but require endogenous Rac 1 and Cdc42Hs activities : coexpression of a dominant negative Rac 1 impairs membrane ruffling and lamellipodia but not filopodia or microvilli formation . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
This supports the existence of an essential functional link , previously suggested by biochemical studies , between Cdc 42 , WAS protein ( WASp ) and the actin cytoskeleton in primary human macrophages . ^^^ Moreover , these data suggest that Cdc 42 WASp mediated filopodial extension is a requirement for chemotaxis but not for chemokinesis in these cells . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
The Y40C effector mutant of Cdc 42 no longer interacts with many of its known target proteins , such as p 65 ( PAK ) and WASP , yet this mutant can still induce filopodia formation . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
TC 10 stimulated Jun N terminal kinase ( JNK ) and p 21 activated kinase ( PAK ) activities and interacted with a set of effectors ( alpha , beta and gammaPAK , MRCKalpha / beta , MLK 2 , N WASP and MSE 55 ) that overlaps with those for Cdc 42 and Rac . ^^^ It interacts with a similar subset of effectors to Cdc 42 but not with MLK 3 , WASP or ACK 1 . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
WASP contains multiple domains that interact with various signalling proteins , including the guanine triphosphatase ( GTPase ) Cdc42Hs and SH 3 domain containing proteins . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Key signal transducers , such as the small GTPases Cdc 42 and Rac , have now been shown to link via proteins of the WASP family to the Arp2 / 3 complex , which nucleates actin polymerization . . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
These results show that Scar and , likely , related proteins , such as the Cdc 42 targets WASp and N WASp , are endogenous activators of actin polymerization by the Arp2 / 3 complex . . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Inducible recruitment of Cdc 42 or WASP to a cell surface receptor triggers actin polymerization and filopodium formation . ^^^ We have investigated the consequences of local recruitment of activated Cdc 42 or WASP to the plasma membrane . ^^^ The Cdc 42 effector WASP could also induce the formation of protrusions , albeit of different morphology . ^^^ CONCLUSIONS : This is the first demonstration that the local recruitment of activated Cdc 42 or its downstream effector , WASP , to a membrane receptor in whole cells is sufficient to trigger actin polymerization that results in the formation of membrane protrusions . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
The product of the WAS gene , WAS protein ( WASP ) , binds to the small GTPase Cdc 42 . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
IpaC induced extensions were inhibited by a dominant interfering form of Cdc 42 or the Cdc 42 binding domain of WASP , whereas a dominant interfering form of Rac resulted in inhibition of lamellae formation . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
WASp contains a binding motif for the Rho GTPase CDC42Hs as well as verprolin / cofilin like actin regulatory domains , but no specific actin structure regulated by CDC42Hs WASp has been identified . ^^^ We found that WASp colocalizes with CDC42Hs and actin in the core of podosomes , a highly dynamic adhesion structure of human blood derived macrophages . ^^^ These findings indicate that WASp controls podosome assembly and , in cooperation with CDC42Hs , podosome disassembly in primary human macrophages . . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Signalling to actin : the Cdc 42 N WASP Arp2 / 3 connection . ^^^ The molecular link between the signalling pathway regulating the formation of filopodia and the initiation of local actin polymerization has been elucidated : N WASP , a close homologue of WASP , which is the product of the gene responsible for the Wiskott Aldrich syndrome , mediates a direct connection between the small G protein Cdc 42 and the Arp2 / 3 complex . . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Our results show that a CRIB containing peptide from PAK , but not that from N WASP , inhibits growth cone collapse and that the inhibitory activity correlates with binding to Rac 1 and not to Cdc 42 . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
In this pathway , the GTPase Cdc 42 acts in concert with WASP family proteins to activate the Arp2 / 3 complex . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Localization of the PAK 1 , WASP , and IQGAP 1 specifying regions of Cdc 42 . ^^^ Potential effectors of Cdc 42 implicated in mediating its cytoskeletal effect in mammalian cells include PAK 1 , WASP , and IQGAP 1 . ^^^ Site directed mutants of the switch 1 domain and neighboring regions of Cdc 42 demonstrated differential binding patterns toward the PBDs of PAK 1 , WASP , and IQGAP 1 , suggesting that switch 1 provides essential determinants for the effector binding , but recognition of each effector by Cdc 42 involves a distinct mechanism . ^^^ Differing from Rac 1 , the switch 1 domain and the surrounding region ( amino acids 29 to 55 ) of Cdc 42 appeared to be sufficient for specific binding to PAK 1 , whereas determinants outside the switch 1 domain , residues 157 191 and 84 120 in particular , were necessary and sufficient to confer specificity to WASP and IQGAP 1 , respectively . ^^^ In addition , IQGAP 1 , but not PAK 1 nor WASP , required the unique `` insert region , ' ' residues 122 134 , of Cdc 42 to achieve high affinity binding . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Measurements were made of their equilibrium binding constants to the Cdc 42 binding domains of the CRIB effectors ACK , PAK , and WASP and to the GTPase activating protein Rho GAP . ^^^ These mutations are interpreted using the structures of the Cdc42 / ACK and Cdc42 / WASP complexes to give insight into how effectors can specifically recognize Cdc 42 . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
The activity of N WASp is enhanced by the binding of effectors like Cdc 42 guanosine 5 ' 3 O ( thio ) triphosphate , phosphatidylinositol bisphosphate , or the Shigella IcsA protein . ^^^ Cdc 42 and Grb 2 bind simultaneously to N WASp and enhance actin polymerization synergistically . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
The structure is compared with those of Cdc 42 bound to similar fragments of ACK and WASP , two effector proteins that bind only to Cdc 42 . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Here we show that the amino terminal WH 1 domain , and not the polyproline rich region , of N WASP is responsible for its recruitment to sites of actin polymerization during Cdc 42 independent , actin based motility of vaccinia virus . ^^^ Our observations show that vaccinia and Shigella activate the Arp2 / 3 complex to achieve actin based motility , by mimicking either the SH2 / SH3 containing adaptor or Cdc 42 signalling pathways to recruit the N WASP WIP complex . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
N WASP is tightly regulated by multiple signals : Only costimulation by Cdc 42 and phosphatidylinositol ( 4 , 5 ) bisphosphate ( PIP 2 ) yields potent polymerization . ^^^ We found that regulation requires N WASP ' s constitutively active output domain ( VCA ) and two regulatory domains : a Cdc 42 binding domain and a previously undescribed PIP ( 2 ) binding domain . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Assembly of branched actin filament networks at the leading edge of migrating cells requires stimulation of the Arp2 / 3 complex by WASp proteins , in concert with the WASp activators Cdc 42 , PIP ( 2 ) and profilin . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
A novel neural Wiskott Aldrich syndrome protein ( N WASP ) binding protein , WISH , induces Arp2 / 3 complex activation independent of Cdc 42 . ^^^ WISH strongly enhanced N WASP induced Arp2 / 3 complex activation independent of Cdc 42 in vitro , resulting in rapid actin polymerization . ^^^ An N WASP mutant ( H208D ) that can not bind Cdc 42 still induced microspike formation when coexpressed with WISH . ^^^ These findings suggest that WISH activates Arp2 / 3 complex through N WASP dependent and independent pathways without Cdc 42 , resulting in the rapid actin polymerization required for microspike formation . . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
WASP and Ena / VASP family proteins have been reported to regulate the cortical actin cytoskeleton as downstream effectors of the Rho family small G proteins Rac and Cdc 42 , but their functions are little understood . ^^^ N WASP and Cdc 42 were concentrated along the actin filament bundles of microspikes but not at the tips . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Moreover , the Cdc 42 downstream effectors MLK 3 , ACK 1 , PAK 1 , and WASP had no detectable influence on Ras GRF mediated MAPK activation . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Cooperative binding of Cdc 42 and phosphatidylinositol 4 , 5 bisphosphate ( PtdIns ( 4 , 5 ) P ( 2 ) ) exposes the VCA region , activating N WASP . ^^^ In addition to this activation mechanism , WISH also activates N WASP independently of Cdc 42 and PtdIns ( 4 , 5 ) P ( 2 ) , by binding to the proline rich region of N WASP . ^^^ Thus , N WASP , which is activated downstream of Cdc 42 or independently by WISH , induces formation of filopodia and WAVE 2 , which is activated via IRSp 53 downstream of Rac , induces formation of lamellipodia . . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
WASp and N WASP are intrinsically autoinhibited , and their activity is regulated by Rho family GTPases such as Cdc 42 , membrane polyphosphoinositides , WIP / verprolin , and SH 3 domain proteins . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
It is believed that the C terminal Arp2 / 3 complex activating domain ( verprolin homology , cofilin homology , and acidic ( VCA ) or C terminal region of WASP family proteins domain ) of N WASP is usually kept masked ( autoinhibition ) but is opened upon cooperative binding of upstream regulators such as Cdc 42 and phosphatidylinositol 4 , 5 bisphosphate ( PIP 2 ) . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Wasp recruitment to the T cell : APC contact site occurs independently of Cdc 42 activation . ^^^ Cdc 42 and WASP are critical regulators of actin polymerization whose function during T cell signaling is poorly understood . ^^^ Surprisingly , WASP localization was independent of the Cdc 42 binding domain but required the proline rich domain . ^^^ Our results indicate that localized WASP activation requires the integration of multiple signals : WASP is recruited via interaction with SH 3 domain containing proteins and is activated by Cdc 42 GTP concentrated at the same site . . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
We also searched for the Cdc 42 ( V 12 ) target but overexpression of the Cdc 42 effector WASP did not mimic the inhibition of exocytosis observed in cells transfected with the activated GTPase . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
The acidic regions of WASp and N WASP can synergize with CDC42Hs and Rac 1 to induce filopodia and lamellipodia . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
In an analogous pathway , direct interaction of Cdc 42 with the related protein N WASP stimulates actin polymerization . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
WASp is capable of forming an auto inhibited conformation , which can be disrupted by binding of Cdc 42 and phosphatidylinositol 4 , 5 bisphosphate , leading to its activation . ^^^ Here we show that the Src family kinase Hck induces phosphorylation of WASp Tyr ( 291 ) independently of Cdc 42 and that this causes a shift in the mobility of WASp upon SDS PAGE . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Furthermore , overexpression of WASp inhibits anterograde transport of MNK , further supporting regulation by the Cdc 42 GTPase . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
In resting cells , WASP exists in a complex with WIP , which inhibits its activation by Cdc 42 . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
However , in the presence of the active form of the GTPase Cdc 42 ( Cdc42V12 ) , which is thought to switch WASP to an active ' open conformation ' , the amount of WASP associated with the receptor was markedly increased . ^^^ We hypothesize that a transient interaction between C5aR and WASP occurs following the stimulation of C5aR and Cdc 42 activation . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
These discoveries have fuelled interest in understanding both the role of the actin cytoskeleton as an integral component of lymphocyte activation and the interplay between lymphoid cell cell contact sites ( immunological synapse ) , retractile pole structures ( uropod , distal pole complex ) , and Rho family GTPases ( Rac , Rho , Cdc 42 ) , their upstream activators ( Dbl family guanine nucleotide exchange factors ) and their downstream effectors ( WASp , Arp2 / 3 , ADAP ) . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
The Wiscott Aldrich syndrome protein , WASP , is an effector through which cdc 42 , a Rho family GTPase , regulates the actin cytoskeleton in hematopoietic cells . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
This function is controlled by the small GTPase Cdc 42 , which regulates the autoinhibitory loop formation of WASP . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
The EGF stimulated phosphorylation of Cdc 42 is not required for its activation , nor does it directly affect the interactions of activated Cdc 42 with target / effector proteins including PAK , ACK , WASP , or IQGAP . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
WASP and N WASP have functional and physical associations with Cdc 42 , a Rho family small GTPase involved in filopodium formation . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Although the molecular events linking activation of a GTPase to the formation of an actin based process with a characteristic morphology are incompletely understood , Rac GTP is thought to promote the activation of SCAR / WAVE , whereas Cdc 42 is thought to initiate the formation of filopodia through WASP . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Activated GTP bound Cdc 42 dissociates the intramolecular autoinhibitory loop formation of WASP . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
We also showed that the nuclear localization of N WASP is dependent on its being in the open conformation either after its activation by Cdc 42 or the truncation of the C terminal VCA domain . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
The protrusion of two distinct actin containing organelles , lamellipodia and filopodia , is thought to be regulated by two parallel pathways : from Rac 1 through Scar / WAVEs to lamellipodia , and from Cdc 42 through N WASP to filopodia . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
In addition , we provide information on the molecular mechanisms that control WASp function , demonstrating that binding of NK cells to sensitive targets or triggering through CD 16 by means of reverse antibody dependent cellular cytotoxicity ( ADCC ) rapidly activates Cdc 42 . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
WASP is regulated by autoinhibition , and the intramolecular contacts that inactivate the protein can be relieved through binding to the Rho family GTPase Cdc 42 . ^^^ The model is parameterized by the stability of WASP against unfolding and by the Cdc 42 affinities of WASP constructs that mimic the unfolded and folded conformations . ^^^ The model is consistent with NMR spectra of GTPase bound WASP , and accurately predicts changes of amide hydrogen exchange behavior and Cdc 42 affinity as a function of WASP stability . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Similar deletion of the VCA domain of WASP attenuated Cdc 42 V12 mediated SRE activation , suggesting that WAVE 2 acts in relation to Rac as WASP acts in relation to Cdc 42 . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
WASP , Arp 2 / 3 , profilins 1 and 2 , and Cdc 42 , RhoA and RhoB GTPases were localized by indirect immunofluorescence ( IIF ) in guinea pig spermatozoa and their presence corroborated by Western blotting . ^^^ By immunoprecipitation , Cdc 42 WASp association was identified in capacitated but not in noncapacitated gametes . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Cdc 42 binds and activates the WASP proteins , which in turn activate the actin nucleating complex Arp2 / 3 . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
RNA interference and dominant negative mutant expression analyses revealed that neural WASP ( N WASP ) , Arp2 / 3 complex , and their upstream regulators , Nck 1 , Cdc 42 , and WIP , are necessary for invadopodium formation . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Osteoclasts stimulated with osteopontin simulated the effects of Rho and Cdc 42 in phosphatidylinositol 4 , 5 bisphosphate ( PIP 2 ) association with WASP as well as formation of podosomes , peripheral microfilopodia like structures , and actin ring . ^^^ Subsequent interaction of Cdc 42 and Arp2 / 3 with WASP may enhance cortical actin polymerization in the process of actin ring formation in osteoclasts . . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Inhibition of Kit modulated phosphorylation dependent interactions with pathways controlling focal adhesion ( paxillin , leupaxin , p130CAS , FAK 1 , the Src family kinase Lyn , Wasp , Fhl 3 , G25K , Ack 1 , Nap 1 , SH3P12 / ponsin ) and septin actin complexes ( NEDD 5 , cdc 11 , actin ) . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
While some effectors , such as the tyrosine kinase , ACK , and the scaffold protein , WASP , are unique to Cdc 42 , others , such as the serine threonine kinase , PAK , are shared with Rac . ^^^ Previous mutagenesis studies identified Val 42 and Leu 174 as residues that selectively affect binding of Cdc 42 to ACK and WASP but not to PAK . ^^^ None of these mutant Rac proteins bound WASP with a similar affinity to Cdc 42 . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Inhibition or genetic deletion of tyrosine phosphorylation , Nck , WASP interacting protein , and Cdc 42 does not affect M . marinum actin tail formation , excluding the participation of these molecules as upstream activators of N WASP in the initiation of actin based motility . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
In contrast , Cdc 42 and proteins required for F actin assembly ( Arp2 / 3 , WASP , Myosin , alpha actinin ) were retained on phagosomes in a LPG dependent manner . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
Here , we describe a mechanism that ensures rapid and selective long range Cdc 42 WASp recognition . ^^^ The crystal structure of TC 10 , together with mutational and bioinformatic analyses , proved that the basic region of WASp and two unique glutamates in Cdc 42 generate favorable electrostatic steering forces that control the accelerated WASp Cdc 42 association reaction . ^^^ Although Cdc 42 , TC 10 , and other members of the Rho family have been implicated in binding to and activating the WAS proteins , the exact nature of such a protein protein recognition process has remained obscure . ^^^
Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
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Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
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Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
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Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
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Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
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Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
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Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
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Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
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Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
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Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
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Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
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Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
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Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
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Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
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Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
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Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
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Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
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Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
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Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
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Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
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Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
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Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
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Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
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Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
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Interacting proteins: P42768 and P60953 Pubmed SVM Score :0.0
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