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 transmission and neurogenesis. Endocytosis accompanies receptor processing and plays an essential role in attenuating receptor tyrosine kinase signal 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) domain dependent protein-protein interactions are important to tyrosine kinase receptor signal transduction. The C-terminus of dynamin contains two clusters of SH3 domain binding proline motifs; these motifs may interact with known SH3 domain proteins during tyrosine kinase receptor activation. We demonstrate here that SH3 domain-containing signal transduction proteins, such as phospholipase C gamma-1 (PLC gamma-1), do indeed bind to dynamin in a growth factor inducible manner. The induction of PLC gamma-1 binding to dynamin occurs within minutes of the addition of platelet derived growth factor (PDGF) to cells. Binding of these signal transduction proteins to dynamin involves specific sorting to 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 for formation of the protein complex required for the endocytic processing of activated tyrosine kinase receptors.
Scaife
R
R
Institut de Biologie Structurale, Grenoble, France.
Gout
I
I
Waterfield
M D
MD
Margolis
R L
RL
D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D016384:Consensus Sequence / Q000235:genetics; D034281:Dynamins; D066246:ErbB Receptors / Q000378:metabolism*; D051380:GRB2 Adaptor Protein; D020558:GTP Phosphohydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016716:PC12 Cells; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases; D051966:Phospholipase C gamma; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011392:Proline / Q000502:physiology; D011485:Protein Binding; D011506:Proteins / Q000032:analysis / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013379:Substrate Specificity; D010738:Type C Phospholipases / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C495949:Grb2 protein, mouse; D007527:Isoenzymes; D010455:Peptides; D010982:Platelet-Derived Growth Factor; D011506:Proteins; D011993:Recombinant Fusion Proteins; D011392:Proline; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D020558:GTP Phosphohydrolases; D034281:Dynamins