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Alternative splicing removes the SH2-binding motif of Disabled homolog 1 (Dab1), abrogating binding to Adapter molecule crk (Crk). Both Adapter molecule crk (Crk) and Crk-like protein (Crkl) bind equally well to variants 2 and 3. The authors theorise that since Adapter molecule crk (Crk) is directly linked to the C3G-Rap1 pathway, and NCK2-beta is linked to the Breast cancer anti-estrogen resistance protein 1 (Bcar1) (p130Cas) pathway, it is likely that isoforms 2 and 3 connect to different downstream cascades. It was suggested that the ability of different Dab1 isoforms to recruit distinct sets of SH2 domains implies a fine-tuning role of Dab1 splicing in the intricate series of events that underlie neuronal migration (Gao et al. (2012) (here)) (See also Katyal and Godbout (2004) (here) and Gao et al. (2010) (here)).

(1) Disabled homolog 1 (Dab1)
(2) Adapter molecule crk (Crk)

Interaction #1 Dab1 - Crk

(1) ELM:LIG_SH2_IA motif (220YQVP223) in Disabled homolog 1 (Dab1)
(2) SH2 domain (13-118) in Adapter molecule crk (Crk)

Interaction Regulation
Alternative splicing Abrogation (Phosphorylation of Y220 on Disabled homolog 1 (Dab1)) of the Disabled homolog 1 (Dab1) LIG_SH2_IA motif - Adapter molecule crk (Crk) SH2 domain interaction

Regulatory Enzymes for switch
Modifying enzymes for residue: Y220: Neuronal proto-oncogene tyrosine-protein kinase Src (Src)


(1) Splice-mediated motif switching regulates Disabled-1 phosphorylation and SH2 domain interactions.
Gao et al. (2012)

(2) Activation of a Dab1/CrkL/C3G/Rap1 pathway in Reelin-stimulated neurons.
Ballif et al. Curr. Biol. (2004)

(3) Interaction between Dab1 and CrkII is promoted by Reelin signaling.
Chen et al. J. Cell. Sci. (2004)

(4) Tyrosine phosphorylated Disabled 1 recruits Crk family adapter proteins.
Huang et al. Biochem. Biophys. Res. Commun. (2004)

(5) Identification of reelin-induced sites of tyrosyl phosphorylation on disabled 1.
Keshvara et al. J. Biol. Chem. (2001)

See also

Other switches involving participants
Disabled homolog 1 (Dab1) - 10 more (view)
Adapter molecule crk (Crk) - 2 more (view)

Other switches involving interfaces
SH2 domain - 140 more (view)
ELM:LIG_SH2_IA - 16 more (view)

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