Mouse alpha 1-syntrophin binding to Grb2: Further evidence of a role for syntrophin in cell signaling

Syntrophins have been proposed to serve as adapter proteins. Syntrophins ar e found in the dystrophin glycoprotein complex (DGC); defects in the consti tuents of this complex are linked to various muscular dystrophies. Blot ove rlay experiments demonstrate that alpha -dystroglycan, beta -dystroglycan, and syntrophins all bind Grb2, the growth factor receptor bound adapter pro tein. Mouse alpha1-syntrophin sequences were produced as chimeric fusion pr oteins in bacteria and found to also bind Grb2 in a Ca2+-independent manner . This binding was localized to the proline rich sequences adjacent to and overlapping with the N-terminal pleckstrin homology domain (PH1). Grb2 boun d syntrophin with an apparent K-D of 563 +/- 15 nM. Grb2-C-SH3 domain bound syntrophin with slightly higher affinity than Grb2-N-SH3 domain. Crk-L, an SH2/SH3 protein of similar domain structure but different specificity, doe s not bind these syntrophin sequences.