title: The interaction of the tyrosine kinase pp60src with membrane and cytoskeletal components.
abstract: To study the mechanism of oncogenic transformation we have investigated the association of pp60v-src with the cytoskeleton using a variety of mutants. Transformation is associated with the interaction of pp60v-src with the cytoskeleton, specifically in adhesion plaques. Biochemical analysis has shown a correlation between tyrosine-specific phosphorylation of the fibronectin receptor and the loss of surface-bound fibronectin, but no such correlation with phosphorylation of vinculin or talin. The role of the nontransforming protooncogene product pp60c-src was studied in platelets, which express large amounts of this protein. In resting platelets pp60c-src was soluble in detergent-containing buffers, however it became associated with the cytoskeleton, but not the membrane skeleton, after platelet activation. This association was inhibited by EDTA or RGDS peptides and was therefore dependent on occupancy of a platelet integrin, gpIIb/IIIa. The role of pp60c-src-associated tyrosine phosphorylation in platelet activation was also investigated. Inhibitors of tyrosine phosphorylation inhibited integrin-dependent platelet aggregation and second messenger production, indicating a close linkage between matrix receptor occupancy, pp60c-src association with the cytoskeleton and platelet function.
authors.affiliation: Yamanouchi Research Institute, Littlemore Hospital, Oxford, UK.
authors.forename: S
authors.initials: S
authors.lastname: Kellie
authors.forename: A R
authors.initials: AR
authors.lastname: Horvath
authors.forename: G
authors.initials: G
authors.lastname: Felice
authors.forename: R
authors.initials: R
authors.lastname: Anand
authors.forename: C
authors.initials: C
authors.lastname: Murphy
authors.forename: J
authors.initials: J
authors.lastname: Westwick
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism*; D015539:Platelet Activation / Q000502:physiology; D051381:Rats
chemical_list: D015688:Oncogene Protein pp60(v-src)