MOUSE DISABLED (MDAB1) - A SRC BINDING-PROTEIN IMPLICATED IN NEURONALDEVELOPMENT

Here, we identify a mouse homolog of the Drosophila Disabled (Dab) pro tein, mDab1, and show it is an adaptor molecule functioning in neural development. We find that mDab1 is expressed in certain neuronal and h ematopoietic cell lines, and is localized to the growing nerves of emb ryonic mice. During mouse embryogenesis, mDab1 is tyrosine phosphoryla ted when the nervous system is undergoing dramatic expansion. However, when nerve tracts are established, mDab1 lacks detectable phosphotyro sine. Tyrosine-phosphorylated mDab1 associates with the SH2 domains of Src, Fyn and Abl. An interaction between mDab1 and Src is observed wh en P19 embryonal carcinoma (EC) cells undergo differentiation into neu ronal cell types. mDab1 can also form complexes with cellular phosphot yrosyl proteins through a domain that is related to the phosphotyrosin e binding (PTB) domains of the She family of adaptor proteins. The mDa b1 PTB domain binds to phosphotyrosine-containing proteins of 200, 120 and 40 kDa from extracts of embryonic mouse heads. The properties of mDab1 and genetic analysis of Dab in Drosophila suggest that these mol ecules function in key signal transduction pathways involved in the fo rmation of neural networks.