Dab1 (F6E1K) Rabbit mAb #23180

The Reelin signaling pathway plays a critical role in neuronal development. Reelin is a secreted glycoprotein that binds to the lipoprotein receptors VLDLR and ApoER2 or alpha3beta1 integrin on the surface of neurons (1,2). Activation of these receptors induces tyrosine phosphorylation of Disabled 1 (Dab1), an intracellular adaptor. It is generally believed that tyrosine phosphorylation of Dab1 by Src family tyrosine kinases is the most critical downstream event in Reelin signaling. The phosphotyrosine-binding (PTB) domain within its amino terminus enables Dab1 to recognize and bind to a conserved sequence motif within the cytoplasmic tail of the receptors. In addition, the PTB domain contains a pleckstrin homology-like subdomain that binds to phosphoinositides. The phosphoinositide-binding region within the Dab1 PTB domain is required for membrane localization and basal tyrosine phosphorylation of Dab1 independent of VLDLR and ApoER2 (3). It has been demonstrated that Src, CrkII, CrkL, and Dock1 associate with tyrosine-phosphorylated Dab1. The CrkII-Dab1 interaction requires tyrosine phosphorylation of Dab1 at residues 220 or 232 (4).