| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.55979956 |
| A direct interaction between Crkl and Abl has also been shown using a yeast two hybrid screen . . 0.55979956^^^ |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.53157947 |
| We have previously shown that CRKL , but not the related adapter protein c CRK , is tyrosine phosphorylated in cell lines transformed by BCR / ABL , and that CRKL binds to BCR / ABL through the CRKL SH 3 domains . 0.53157947^^^ |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.7096031 |
| In cells expressing the proline deletion mutation of BCR ABL , CRKL is still tyrosine phosphorylated and forms a complex with BCR ABL as demonstrated by coimmunoprecipitation . 0.7096031^^^ CRKL has previously been shown to be a major tyrosine phosphorylated protein in neutrophils of patients with BCR ABL+ chronic myelogenous leukemia and in cell lines expressing BCR ABL CRKL and BCR ABL form a complex as demonstrated by coimmunoprecipitation and are capable of a direct interaction in a yeast two hybrid assay . 0.65013474^^^ |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.88589824 |
| CRKL binds directly to BCR / ABL through its N terminal SH 3 domain , suggesting it may be involved in BCR / ABL signal transduction . 0.88589824^^^ |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.73386734 |
| Crkl binds to BCR / ABL through its N terminal SH 3 domain and is known to interact with several signaling proteins that have been implicated in integrin signaling , including Cbl , Cas , Hef 1 , and paxillin . 0.73386734^^^ |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| Anti CRKL immunoprecipitates from CML cells , but not normal cells , were found to contain p210BCR / ABL and c ABL . ^^^ Using GST CRKL fusion proteins , the SH 3 domains of CRKL were found to bind c ABL and p210BCR / ABL , while the SH 2 domain of CRKL bound to paxillin , suggesting that CRKL could physically link p210BCR / ABL to paxillin . ^^^ |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| CRKL , an adaptor protein consisting of SH 2 and SH 3 domains in the absence of a catalytic domain , is one potential in vivo substrate of BCR / ABL . ^^^ Previous experiments have shown that CRKL is phosphorylated on tyrosine in the chronic myelogenous leukemia ( CML ) cell line K 562 and that CRKL is a substrate for ABL and for BCR / ABL in COS 1 cells . ^^^ In the current study , we show that in peripheral blood cells a direct correlation exists between the presence of BCR / ABL and the phosphorylation status of CRKL . ^^^ This result strongly suggests that CRKL is a biologically significant substrate for BCR / ABL and is likely to play a major role in the development of Ph+ leukemia . . ^^^ |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| Our results suggest that pp 39 CRKL in CML neutrophils may be stably tyrosine phosphorylated by the BCR / ABL kinase at an early stage of myeloid differentiation when the ABL kinase is active . ^^^ |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| We have previously shown that the adaptor molecule Crkl is a major in vivo substrate for the Bcr / Abl tyrosine kinase , and it is thought to connect Bcr / Abl with downstream effectors . ^^^ In the current study , a tyrosine phosphorylated protein with a molecular mass of approximately 120 kDa was identified which binds only to the Crkl Src homology 2 ( SH 2 ) domain in cells , including Ph positive patient material , containing an active Bcr / Abl protein . ^^^ The Src homology 3 ( SH 3 ) domains of Crkl do not bind to Cbl , but do bind Bcr / Abl . ^^^ These findings suggest the existence of a trimolecular complex involving Bcr / Abl , Crkl , and Cbl and are consistent with a model in which Crkl mediates the oncogenic signal of Bcr / Abl to Cbl . . ^^^ |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| In the current study , we show that CRKL is highly phosphorylated in the chronic myelogenous leukemia cell line K 562 and that it is a substrate for the p 210 BCR / ABL and p 145 ABL kinases . ^^^ BCR / ABL and ABL are coimmunoprecipitated with CRKL in vivo , demonstrating that relatively stable complexes are formed . ^^^ BCR / ABL and ABL are coimmunoprecipitated with CRKL in vivo , demonstrating that relatively stable complexes are formed . ^^^ |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| In vitro binding studies indicated that the SH 2 domains of CRKL and c CRK bound directly to p120CBL , while the SH 3 domains of c CRK and CRKL bound to BCR / ABL and c ABL . ^^^ These data suggest that BCR / ABL may induce the formation of multimeric complexes of signaling proteins which include p120CBL , PI3K , c CRK or CRKL , c ABL and BCR / ABL itself . . ^^^ The proto oncogene product p120CBL and the adaptor proteins CRKL and c CRK link c ABL , p190BCR / ABL and p210BCR / ABL to the phosphatidylinositol 3 ' kinase pathway . ^^^ |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| The two major sites of cbl tyrosine phosphorylation in abl transformed cells select the crkL SH 2 domain . ^^^ These sites conform to the preferred abl kinase substrate sequence of YXXP and we show that following phosphorylation they mediate an association with the crkL SH 2 domain . . ^^^ |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| Tyrosine 207 in CRKL is the BCR / ABL phosphorylation site . ^^^ The SH2 / SH3 adapter protein CRKL is a major substrate of the deregulated BCR / ABL tyrosine kinase and is aberrantly tyrosine phosphorylated in Ph positive leukemia cells . ^^^ In an in vitro kinase assay , CRKL phosphorylation by the abl kinase was limited to a small region between the two CRKL SH 3 domains . ^^^ Within this region , mutation of tyrosine residue 207 yielded a mutant CRKL which could not be phosphorylated by BCR / ABL . ^^^ |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| The BCR / ABL oncogene alters interaction of the adapter proteins CRKL and CRK with cellular proteins . ^^^ In cell lines transformed by BCR / ABL , CRKL was tyrosine phosphorylated , while CRK was not . ^^^ We looked for changes in CRK and CRKL binding proteins in Ba / F3 hematopoietic cell lines which were transformed by BCR / ABL . ^^^ After BCR / ABL transformation , the CRKL SH 3 domain binding proteins did not change , with the exception that BCR / ABL now coprecipitated with CRKL . ^^^ After BCR / ABL transformation , both the CRKL and CRK SH 2 domains bound to a new complex of proteins of approximate molecular weight 105 120 kDa . ^^^ |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| CRKL is an SH 2 SH3 SH 3 adapter protein that is a major substrate of the BCR / ABL oncogene . ^^^ In cells transformed by BCR / ABL we have previously shown that CRKL is associated with two focal adhesion proteins , tensin and paxillin , suggesting that CRKL could be involved in integrin signaling . ^^^ In both cell types , CRKL is constitutively complexed to C3G , SOS , and c ABL through its SH 3 domains , and the stoichiometry of these complexes does not change upon integrin ligation . ^^^ |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| Interactions of CBL with BCR ABL and CRKL in BCR ABL transformed myeloid cells . ^^^ Since CRKL , an SH 2 , SH 3 domain containing adapter protein is known to bind directly to BCR ABL and also binds to tyrosine phosphorylated c CBL , the ability of CRKL to mediate a complex between c CBL and BCR ABL was examined . . ^^^ |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| The major target proteins have been identified , and are very similar to the known substrates of BCR / ABL , including Shc , CBL , CRKL , and several proteins in the cytoskeleton . ^^^ |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| BCR / ABL induced leukemogenesis causes phosphorylation of Hef 1 and its association with Crkl . ^^^ The adaptor molecule Crkl is a major in vivo substrate of the deregulated Bcr / Abl tyrosine kinase and functions as a molecular link with other signaling proteins . ^^^ While associated in vivo with Bcr / Abl through its SH 3 domain , Crkl can interact simultaneously via its SH 2 domain with other tyrosine phosphorylated proteins . ^^^ This supports a model in which Crkl acts as mediator between Bcr / Abl and downstream effectors . ^^^ |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| Role of the adapter protein CRKL in signal transduction of normal hematopoietic and BCR / ABL transformed cells . ^^^ CRKL is a prominent substrate of the BCR / ABL oncoprotein in chronic myelogenous leukemia and binds to both BCR / ABL and c ABL . ^^^ Structurally , the amino terminal SH 3 domain of CRKL has been shown to bind proteins such as C3G , SOS , PI 3 K , c ABL or BCR / ABL . ^^^ |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| Crkl is an adapter protein and phosphotyrosine containing substrate implicated in transformation by the bcr abl oncogene and in signaling by cytokines . ^^^ In vivo and in vitro tryptic phosphopeptide mapping studies show that Crkl is phosphorylated on multiple tyrosine residues when overexpressed or when activated by Bcr Abl . ^^^ |
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| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| In 32D myeloid cells and Rat 1 fibroblasts transformed by p 210 ( bcr abl ) , p 62 ( dok ) is tyrosine phosphorylated and co immunoprecipitates with Bcr Abl , RasGAP , and CrkL , a Src homology 2 ( SH 2 ) and SH 3 domain containing adaptor protein . ^^^ Tyrosine phosphorylated p 62 ( dok ) from cells expressing p 210 ( bcr abl ) bound directly to the SH 2 domains of Abl and CrkL in a gel overlay assay . ^^^ However , in a gel overlay assay , p 62 ( dok ) from cells expressing the SH 2 domain deletion was incapable of associating directly with SH 2 domains of Abl and CrkL . ^^^ |
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| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| In contrast , 3T3 cells stably transfected with Bcr / Abl P 210 show a prominent reduction in the amount of C3G complexed to Crkl and do not exhibit tyrosine phosphorylation of C3G upon spreading and attachment . ^^^ These data establish that integrin mediated cell adhesion results in Crkl mediated tyrosine phosphorylation of C3G , a pathway which can be disrupted by Bcr / Abl . . ^^^ |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| BCR ABL oncoprotein is expressed by platelets from CML patients and associated with a special pattern of CrkL phosphorylation . ^^^ Constitutive tyrosine phosphorylation of CrkL was recently demonstrated in platelets from chronic myelogenous leukaemia ( CML ) patients but BCR ABL tyrosine kinase could not be detected in the platelet lysates . ^^^ Immunoblotting of p210BCR ABL positive platelets lysates with anti CrkL antibody revealed a CrkL triplet consisting of one unphosphorylated and two phosphorylated forms of the protein . ^^^ This CrkL phosphorylation pattern was not observed in normal platelets or CML platelets treated with ABL tyrosine kinase inhibitor CGP57148B . ^^^ The presence of BCR ABL provides an explanation for the constitutive tyrosine phosphorylation of CrkL in CML platelets . ^^^ |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| Upon treatment with CGP 57148 , CRKL , a specific substrate for BCR ABL that propagates signals via phosphatidylinositol 3 ' kinase ( PI3K ) , was dephosphorylated , indicating inhibition of BCR ABL tyrosine kinase at the cellular level . ^^^ |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| The absence of crkl tyrosine phosphorylation , no activation of the abl kinase as measured by autophosphorylation , and a normal size abl transcript suggest an alternative mechanism for leukemogenesis to that operative in Ph positive BCR / ABL positive chronic myeloid leukemia . ^^^ |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| Similar to Bcr Abl , Tel Abl was found in complexes with the adapter protein CRKL . ^^^ In addition , c Crk 2 and CRKL are tyrosine phosphorylated and complexed with numerous other tyrosine phosphorylated proteins in Tel Abl expressing Ba / F3 cells . ^^^ |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| We found that PD 180970 inhibited in vivo tyrosine phosphorylation of p210Bcr Abl ( IC 50 = 170 nM ) and the p210BcrAbl substrates Gab 2 and CrkL ( IC 50 = 80 nM ) in human K 562 chronic myelogenous leukemic cells . ^^^ |
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| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| In addition , Tec and Lyn were shown to phosphorylate Dok 1 , whereas phosphorylated Dok 1 was demonstrated to bind to the SH 2 domains of several signaling molecules activated by SCF , including Abl , CrkL , SHIP , and PLCgamma 1 , but not those of Vav and Shc . ^^^ |
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| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| BCR / ABL P 190 transgenic mice develop leukemia in the absence of Crkl . ^^^ Multiple independent studies have implicated Crkl , a small adapter protein , in transduction of oncogenic signals of Bcr / Abl and Crkl tyrosine phosphorylation is used as a diagnostic tool for Philadelphia positive leukemia . ^^^ We found that the overall survival of P 190 BCR / ABL crkl / mice was comparable to that of genetically matched P 190 BCR / ABL crkl + / + mice . ^^^ |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| These included changes on Crkl , Ras GAP binding protein 1 , and for BCR / ABL , cytoskeletal proteins such as tubulin , and Nedd 5 . ^^^ |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| Furthermore , ex vivo treatment of leukemic cells with imatinib significantly reduced tyrosine phosphorylation of CrkL , a target of the BCR / ABL kinase . ^^^ |
|
| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| Interaction of Bcr / Abl with C3G , an exchange factor for the small GTPase Rap 1 , through the adapter protein Crkl . ^^^ The adapter protein Crkl is one of the most prominently tyrosine phosphorylated substrates of Bcr / Abl in cells and tissues isolated from such patients . ^^^ Here , we report that Crkl mediates the formation of protein complexes that include C3G and Bcr / Abl . ^^^ Co expression of Crkl and C3G with Bcr / Abl generated increased levels of activated Rap 1 . ^^^ |
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| Interacting proteins: P46109 and P00519 |
Pubmed |
SVM Score :0.0 |
| A novel C3G isoform , designated p87C3G , lacking the most amino terminal region of the cognate protein has been found to be overexpressed in two CML cell lines , K 562 and Boff 210 , both expressing Bcr Abl p 210 . p87C3G expression is also highly augmented in patients diagnosed with chronic myeloid leukemia ( CML ) Ph+ , in comparison with healthy individuals , and returns to basal levels after treatment with STI 571 . p87C3G co immunoprecipitates with both CrkL and Bcr Abl in CML cell lines and co immunoprecipitation between p87C3G and Bcr Abl was also detected in primary cells from CML patients . ^^^ |
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