GROWTH FACTOR-INDUCED BINDING OF DYNAMIN TO SIGNAL-TRANSDUCTION PROTEINS INVOLVES SORTING TO DISTINCT AND SEPARATE PROLINE-RICH DYNAMIN SEQUENCES

Dynamin, a 100 kDa GTPase, is critical for endocytosis, synaptic trans mission and neurogenesis. Endocytosis accompanies receptor processing and plays an essential role in attenuating receptor tyrosine kinase si gnal transduction. Dynamin has been demonstrated to be involved in the endocytic processing at the cell surface and may play a general role in coupling receptor activation to endocytosis. Src homology (SH) doma in dependent protein - protein interactions are important to tyrosine kinase receptor signal transduction. The C-terminus of dynamin contain s two clusters of SH3 domain binding proline moths; these moths may in teract with known SH3 domain proteins during tyrosine kinase receptor activation. We demonstrate here that SH3 domain-containing signal tran sduction proteins, such as phospholipase C gamma-1 (PLC gamma-1), do i ndeed bind to dynamin in a growth factor inducible manner. The inducti on of PLC gamma-1 binding to dynamin occurs within minutes of the addi tion of platelet derived growth factor (PDGF) to cells. Binding of the se signal transduction proteins to dynamin involves specific sorting t o individual proline motif clusters and appears to be responsible for co-immunoprecipitation of tyrosine phosphorylated PDGF receptors with dynamin following PDGF stimulation of mammalian cells. The binding of dynamin to SH3 domain-containing proteins may therefore be important f or formation of the protein complex required for the endocytic process ing of activated tyrosine kinase receptors.