Switch #: SWTI000620

Switch type: Binary

Switch subtype: Pre-translational

Description:
Alternative splicing removes the SH2-binding motif of Disabled homolog 1 (Dab1), abrogating binding to Neuronal proto-oncogene tyrosine-protein kinase Src (Src). Splice variants 2 and 3 (only containing one of the YQxI motifs, i.e. Y185 and Y198) exhibit decreased tyrosine phosphorylation, suggesting both motifs are required for full activation of Dab1. Dab1 is likely to recruit Neuronal proto-oncogene tyrosine-protein kinase Src (Src) via these two YQxI motifs, which subsequently phosphorylates adjacent YxVP motifs (here). This was also suggested for Phosphatidylinositol 3-kinase regulatory subunit alpha (Pik3r1) and Suppressor of cytokine signaling 2 (Socs2). Gao et al. (2012) (here) suggests that the ability of different Dab1 isoforms to recruit distinct sets of SH2 domains allows a fine-tuning role for Dab1 splicing in the intricate series of events that underlie neuronal migration (See also Katyal & Godbout (2004) (here) and Gao et al. (2010) (here)).

Participants:
(1) Disabled homolog 1 (Dab1)
(2) 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) Identification of reelin-induced sites of tyrosyl phosphorylation on disabled 1.
Keshvara et al. J. Biol. Chem. (2001)

Other switches involving participants
Disabled homolog 1 (Dab1) - 10 more (view)
Neuronal proto-oncogene tyrosine-protein kinase Src (Src) - 4 more (view)

Other switches involving interfaces
SH2 domain - 140 more (view)
LIG_SH2_SRC - 8 more (view)