| First Author | Huang Y | Year | 2005 |
| Journal | Biochem Biophys Res Commun | Volume | 331 |
| Issue | 4 | Pages | 1460-8 |
| PubMed ID | 15883038 | Mgi Jnum | J:98290 |
| Mgi Id | MGI:3577804 | Doi | 10.1016/j.bbrc.2005.04.064 |
| Citation | Huang Y, et al. (2005) Signaling through Disabled 1 requires phosphoinositide binding. Biochem Biophys Res Commun 331(4):1460-8 |
| abstractText | The Reelin signaling pathway plays a critical role in the correct positioning of neurons within the developing brain. Within this pathway, Disabled 1 (Dab1) serves as an intracellular adaptor that is tyrosine phosphorylated when Reelin, a secreted glycoprotein, binds to the lipoprotein receptors VLDLR and ApoER2 on the surface of neurons. The phosphotyrosine-binding (PTB) domain within its amino terminus enables Dab1 to recognize and bind to a conserved sequence motif within the cytoplasmic tails of the receptors. In addition, the PTB contains a Pleckstrin Homology-like subdomain that binds to phosphoinositides. Here, we show that the phosphoinositide-binding region within Dab1 PTB domain is required for membrane localization and basal tyrosine phosphorylation of Dab1 independently of VLDLR and ApoER2. Furthermore, receptor-independent membrane targeting of Dab1 is required for its interaction with Src and Crk, and disruption of phosphoinositide binding also blocks subsequent Reelin-induced tyrosine phosphorylation of Dab1. |
