Reactome | FYN phosphorylates DAB1 in RELN:VLDLR:DAB1:SH3KBP1

FYN phosphorylates DAB1 in RELN:VLDLR:DAB1:SH3KBP1

Stable Identifier

R-HSA-8855237

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, extracellular region, plasma membrane

ReviewStatus

5/5

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FYN phosphorylates DAB1 in RELN:VLDLR:DAB1:SH3KBP1

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One of the three domains in disabled homolog 1 (DAB1) is a tyrosine-rich region consists of five highly conserved tyrosine residues; Y185, Y198, Y200, Y220 and Y232. These residues correspond to two consensus Src family kinase recognition sites (YQxI, Y185 and Y198) and two consensus Abl/Crk recognition sites (YxVP, Y220 and Y232). At least three of the tyrosine residues (Y198, Y220 and Y232) can be phosphorylated by the Src kinase family member, tyrosine protein kinase fyn (FYN) in response to Reelin (RELN) stimulation (Katyal et al. 2007). Tyrosine-phosphorylated DAB1 acts as a hub to recruit different Src homology 2 (SH2) domain-containing proteins, including the p85 regulatory subunit of phosphatidylinositide-3-kinase (PI3K), cellular adaptors CrkL, Crk, Nck-beta and SOCS (suppressor of cytokine signaling) (Gao & Godbout 2013). Tyrosine phosphorylation of DAB1 also appears to strengthen the association of DAB1 with SH3KBP1 (aka CIN85), an adaptor protein involved in endocytic down-regulation of receptor-tyrosine kinases (Fuchigami et al. 2013).

Literature References

PubMed ID	Title	Journal	Year
23052211	Reelin-Disabled-1 signaling in neuronal migration: splicing takes the stage Gao, Z, Godbout, R	Cell. Mol. Life Sci.	2013
23506116	Dab1-mediated colocalization of multi-adaptor protein CIN85 with Reelin receptors, ApoER2 and VLDLR, in neurons Hisanaga, S, Fukuda, M, Tomita, Y, Hattori, M, Tsuchiya, Y, Nakajima, K, Takano, T, Sato, Y, Saito, T, Kubo, K, Fuchigami, T, Miyauchi, SY	Genes Cells	2013
16529723	Modulation of Reelin signaling by Cyclin-dependent kinase 5 Ohshima, T, Suzuki, H, Ogawa, M, Mikoshiba, K, Morimura, T	Brain Res.	2007
17350651	Hierarchical disabled-1 tyrosine phosphorylation in Src family kinase activation and neurite formation Katyal, S, Glubrecht, D, Monckton, E, Gao, Z, Godbout, R	J. Mol. Biol.	2007