The p60c-src family of protein-tyrosine kinases: structure, regulation, and function.
In 1911, Peyton Rous reported that a fibrosarcoma could be transmitted between chickens in a cell-free extract of the tumor. The transmissible agent, Rous sarcoma virus (RSV), transforms cells by virtue of the presence within its genome of a viral oncogene, v-src, which is derived from a normal cellular gene that has been picked up, or transduced, by the virus. This cellular proto-oncogene, c-src, encodes a protein, p60c-src, which has the ability to phosphorylate proteins on tyrosine residues. Studies of RSV were thus directly responsible for the discovery of cellular proto-oncogenes and of protein-tyrosine kinases, discoveries which have been fundamental in shaping our ideas about cellular growth control. In spite of this, the normal biological role of p60c-src is still unclear and it remains impossible to provide a full answer to the question of how RSV causes tumors. It is clear, however, that c-src is the prototype of a family of at least 8 closely related genes encoding protein tyrosine kinases, the other family members being blk, c-fgr, fyn, hck, lck, lyn, and c-yes. The purpose of this review is to outline our current knowledge of the structure, expression pattern, and function of each of the members of the c-src gene family and to describe recent data which begins to explain how these proteins interact with other cellular proteins to control cell behavior. The evidence for involvement of these proteins in oncogenesis is also discussed.
Brickell
P M
PM
Department of Biochemistry and Molecular Biology, University College and Middlesex School of Medicine, London, U.K.
D000595:Amino Acid Sequence; D000818:Animals; D001773:Blood Cells / Q000378:metabolism; D002874:Chromosome Mapping; D005786:Gene Expression Regulation; D016391:Genes, src / Q000235:genetics*; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008969:Molecular Sequence Data; D015688:Oncogene Protein pp60(v-src) / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051076:Proto-Oncogene Proteins c-fyn; D051575:Proto-Oncogene Proteins c-yes; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000502:physiology*; D017385:Sequence Homology; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic; D019061:src-Family Kinases
C000715470:MAS1 protein, human; D010982:Platelet-Derived Growth Factor; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D015688:Oncogene Protein pp60(v-src); D051076:Proto-Oncogene Proteins c-fyn; D051575:Proto-Oncogene Proteins c-yes; D016392:Proto-Oncogene Proteins pp60(c-src); D019061:src-Family Kinases