FYN phosphorylates DAB1 in RELN:VLDLR:DAB1:SH3KBP1

Stable Identifier
R-HSA-8855237
Type
Reaction [transition]
Species
Homo sapiens
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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
23506116 Dab1-mediated colocalization of multi-adaptor protein CIN85 with Reelin receptors, ApoER2 and VLDLR, in neurons

Fuchigami, T, Sato, Y, Tomita, Y, Takano, T, Miyauchi, SY, Tsuchiya, Y, Saito, T, Kubo, K, Nakajima, K, Fukuda, M, Hattori, M, Hisanaga, S

Genes Cells 2013
23052211 Reelin-Disabled-1 signaling in neuronal migration: splicing takes the stage

Gao, Z, Godbout, R

Cell. Mol. Life Sci. 2013
16529723 Modulation of Reelin signaling by Cyclin-dependent kinase 5

Ohshima, T, Suzuki, H, Morimura, T, Ogawa, M, Mikoshiba, K

Brain Res. 2007
17350651 Hierarchical disabled-1 tyrosine phosphorylation in Src family kinase activation and neurite formation

Katyal, S, Gao, Z, Monckton, E, Glubrecht, D, Godbout, R

J. Mol. Biol. 2007
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Catalyst Activity
Title
protein tyrosine kinase activity of FYN [cytosol]
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Activity
Orthologous Events
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