| Interacting proteins: O75553 and P12931 |
Pubmed |
SVM Score :0.50653915 |
| Furthermore , receptor independent membrane targeting of Dab 1 is required for its interaction with Src and Crk , and disruption of phosphoinositide binding also blocks subsequent Reelin induced tyrosine phosphorylation of Dab1 . . 0.50653915^^^ |
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| Interacting proteins: O75553 and P12931 |
Pubmed |
SVM Score :0.0 |
| Here we report that , although Src can phosphorylate all five tyrosines in vitro , Tyr ( 198 ) and Tyr ( 220 ) represent the major sites of Reelin induced Dab 1 phosphorylation in embryonic neurons . . ^^^ |
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| Interacting proteins: O75553 and P12931 |
Pubmed |
SVM Score :0.0 |
| RESULTS : We found that Reelin induced Dab 1 tyrosine phosphorylation in neuron cultures is inhibited by acute treatment with pharmacological inhibitors of Src family , but not Abl family , kinases . ^^^ In addition , Reelin stimulates Src family kinases by a mechanism involving Dab 1 . ^^^ We analyzed the Dab 1 protein level and tyrosine phosphorylation stoichiometry by using brain samples and cultured neurons that were obtained from mouse embryos carrying mutations in Src family tyrosine kinases . ^^^ |
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| Interacting proteins: O75553 and P12931 |
Pubmed |
SVM Score :0.0 |
| RESULTS : We show that Reelin activates members of the Src family of non receptor tyrosine kinases ( SFKs ) and that this activation is dependent on the Reelin receptors apoER 2 and VLDLR and the adaptor protein Dab 1 . ^^^ |
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| Interacting proteins: O75553 and P12931 |
Pubmed |
SVM Score :0.0 |
| Reelin signaling requires activation of Src family kinases as well as tyrosine phosphorylation of the intracellular adaptor protein Disabled 1 ( Dab 1 ) . ^^^ Here we demonstrate that PI3K activation by Reelin requires Src family kinase activity and depends on the Reelin triggered interaction of Dab 1 with the PI3K regulatory subunit p85alpha . ^^^ |
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| Interacting proteins: O75553 and P12931 |
Pubmed |
SVM Score :0.0 |
| However , Reelin has recently been shown to activate the phosphoinositide 3 kinase ( PI 3 K ) dependent kinase , Akt , as well as Src family kinases in wild type but not Dab 1 / primary embryonic neuronal cultures . ^^^ Using pharmacological inhibitors and mice harboring mutant alleles of Dab 1 , we show here that tyrosine phosphorylation , but not the carboxyl terminal region , of Dab 1 is required for Reelin induced activation of Akt and Src family kinases . ^^^ These results define the first molecular events strictly dependent on Reelin induced Dab 1 tyrosine phosphorylation , and suggest that propagation of the Reelin signal is mediated by Akt , substrates of Src family kinases and / or unidentified molecules that share with these a common molecular link to phosphorylated Dab1 . . ^^^ |
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| Interacting proteins: O75553 and P12931 |
Pubmed |
SVM Score :0.0 |
| Dab 1 function in vivo depends on tyrosine phosphorylation , which is stimulated by extracellular Reelin and requires Src family kinases . ^^^ We have made use of mouse embryo cortical neuron cultures in which Reelin induces Dab 1 tyrosine phosphorylation and Src family kinase activation . ^^^ |
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| Interacting proteins: O75553 and P12931 |
Pubmed |
SVM Score :0.0 |
| These agents induce Dab 1 phosphorylation , activate members of the Src family of nonreceptor tyrosine kinases , modulate protein kinase B / Akt phosphorylation , and increase long term potentiation in hippocampal slices . ^^^ |
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| Interacting proteins: O75553 and P12931 |
Pubmed |
SVM Score :0.0 |
| A key difference between the two forms is the exclusion in chDab 1 E of two Src related tyrosine kinase recognition sites implicated in Reelin mediated Dab 1 tyrosine phosphorylation . ^^^ |
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| Interacting proteins: O75553 and P12931 |
Pubmed |
SVM Score :0.0 |
| Reelin stimulates phosphorylation of Dab 1 on tyrosines 198 and 220 , and phosphorylated Dab 1 is likely to interact with downstream signaling proteins that contain Src homology 2 ( SH 2 ) domains . ^^^ We further show that Crk 1 and Crk 2 , but not CrkL , stimulate phosphorylation of Dab 1 on tyrosine 220 in a Src dependent manner . ^^^ |
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| Interacting proteins: O75553 and P12931 |
Pubmed |
SVM Score :0.0 |
| It is generally believed that tyrosine phosphorylation of Disabled 1 ( Dab 1 ) by Src family tyrosine kinases is the most critical downstream event in Reelin signaling . ^^^ When Src family tyrosine kinases were inhibited , internalization of Reelin was severely abrogated , and Reelin colocalized with Dab 1 near the plasma membrane for a prolonged period . ^^^ |
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| Interacting proteins: O75553 and P12931 |
Pubmed |
SVM Score :0.0 |
| Reelin , a large protein that regulates neuronal migration during embryonic development , activates a conserved signaling pathway that requires its receptors , very low density lipoprotein receptor and apolipoprotein E receptor 2 , the cytoplasmic adaptor protein Disabled 1 ( Dab 1 ) , and Src family kinases ( SFK ) . ^^^ |
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| Interacting proteins: O75553 and P12931 |
Pubmed |
SVM Score :0.0 |
| Biochemical and in vitro experiments implicate Src and Fyn in the Reelin dependent tyrosine phosphorylation of Dab 1 , which controls the positioning of radially migrating neurons in many brain regions . ^^^ Here , we report that , although Src is dispensable and although the absence of Fyn causes an intermediate phenotype , the combined absence of Src and Fyn almost abolishes tyrosine phosphorylation of Dab 1 and causes defects in the fetal cortex and cerebellum very similar to those of dab 1 mutants of the same age . ^^^ |
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| Interacting proteins: O75553 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O75553 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O75553 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O75553 and P12931 |
Pubmed |
SVM Score :0.0 |
| NA |
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