Function, location, and regulation of the src protein-tyrosine kinase.
The physiological roles, precise locations, and relevant targets of the 60 kD protein-tyrosine kinase encoded by viral and cellular src genes p60src are not known, despite intensive study. We describe recent work that bears upon these unresolved problems: (i) p60c-src is phosphorylated during mitosis on threonine and serine residues by the protein kinase encoded by the mammalian homologue of cdc2, suggesting that c-src may contribute to the phenotype of mitotic cells; (ii) multiple regions in the amino-terminal portion of p60src are required for its proper intracellular localization--a short signal for myristylation and signals for association with cytoplasmic granules and with perinuclear and plasma membranes; and (iii) regions (called SH3 and SH2) upstream of the kinase domain modulate the behavior of p60src in complex ways, with some mutations in SH2 rendering p60 host-dependent for transformation. The latter mutants may prove to be powerful tools for identifying proteins that modify or serve as targets for src-encoded protein-tyrosine kinases.
Varmus
H
H
Department of Microbiology, University of California, San Francisco 94143.
Hirai
H
H
Morgan
D
D
Kaplan
J
J
Bishop
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002478:Cells, Cultured; D002645:Chickens / Q000235:genetics / Q000378:metabolism; D016391:Genes, src; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008938:Mitosis; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics / Q000502:physiology*
D008565:Membrane Proteins; D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src); D016392:Proto-Oncogene Proteins pp60(c-src); D016203:CDC2 Protein Kinase