DYNAMIN BINDS TO SH3 DOMAINS OF PHOSPHOLIPASE C-GAMMA AND GRB-2

Src homology 3 (SH3) domains are found in a variety of proteins that a re involved in signal transduction or represent components of the cyto skeleton. These domains are thought to serve as modules that mediate s pecific protein-protein interactions that include prolinerich sequence s on the target protein. We have identified proteins of 110, 80, 65, a nd 43 kDa in human embryonic fibroblasts that bind specifically to the SH3 domain of phospholipase C gamma, a primary substrate of receptor tyrosine kinases, and characterized the 110-kDa band as the microtubul e-activated GTPase dynamin. In addition, dynamin binds the son of seve nless adaptor protein GRB-2 with even higher affinity. This interactio n does not require the dynamin GTPase function and involves a proline- rich target sequence between residues 812 and 820 of dynamin.