Functions of the v-Src protein tyrosine kinase.
The peripheral non-receptor tyrosine kinase oncoprotein, v-Src, has pleiotropic effects. It is a mitogen for quiescent cells, substituting for both competence and progression factor-mediated signals but it also induces cellular morphological transformation. We are dissecting the activities of v-Src by studying mutant proteins, including those with temperature sensitive (ts) effects, in different cellular backgrounds. Activation of a ts v-Src kinase rapidly increases activity of both the transcription factor, AP-1, and MAP kinase, an enzyme that enhances AP-1 activity by both phosphorylation of c-Jun and increased c-fos transcription; the relative contribution of these two events depends on the cells in which v-Src is expressed. Transient early AP-1 activation requires proper location of v-Src at the cell periphery and it is essential for mitogenesis. It is not, however, sufficient for entry into S-phase, there being a second need for v-Src later in G1. Transformation by v-Src does not require AP-1 activation but seems linked to events at the cell periphery, notably phosphorylation of proteins that bind to the v-Src SH3 domain such as the p85 subunit of PI-3 kinase.
Fincham
V
V
Beatson Institute for Cancer Research Cancer Research Campaign Beatson Laboratories, Bearsden, Glasgow, Scotland, UK.
Frame
M
M
Haefner
B
B
Unlu
M
M
Wyke
A
A
Wyke
J
J
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004789:Enzyme Activation; D019950:Mitogen-Activated Protein Kinase 1; D008938:Mitosis; D008954:Models, Biological; D009154:Mutation / Q000502:physiology; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism
D016755:Proto-Oncogene Proteins c-jun; D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src); D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1