|Tyrosine-protein kinase transforming protein Src|
|Chromosome||viral: 0.01 - 0.01 Mb|
The src gene is oncogenic as it triggers uncontrolled growth in abnormal host cells. It was the first retroviral oncogene to be discovered. The src gene was taken up by RSV and incorporated into its genome conferring it with the advantage of being able to stimulate uncontrolled mitosis of host cells, providing abundant cells for fresh infection.
Francis Peyton Rous first proposed that viruses can cause cancer. He proved it in 1911 and was later awarded the Nobel prize in 1966. Chickens grow a tumor called a fibrosarcoma. Rous collected and ground up these sarcomas, and then centrifuged them to remove the solid material. Next, the remaining liquid mixture was injected into chicks. The chicks developed sarcomas. The causative agent in the liquid was a virus, this is now called the Rous sarcoma virus (RSV).
A function for Src tyrosine kinases in normal cell growth was first demonstrated with the binding of family member p56lck to the cytoplasmic tail of the CD4 and CD8 co-receptors on T-cells. Src tyrosine kinases also transmit integrin-dependent signals central to cell movement and proliferation. Hallmarks of v-Src induced transformation are rounding of the cell and the formation of actin rich podosomes on the basal surface of the cell. These structures are correlated with increased invasiveness, a process thought to be essential for metastasis.
v-Src lacks the C-terminal inhibitory phosphorylation site (tyrosine-527), and is therefore constitutively active as opposed to normal Src (c-Src) which is only activated under certain circumstances where it is required (e.g. growth factor signaling). v-Src is therefore an instructive example of an oncogene whereas c-Src is a proto-oncogene.
The first sequence of v-Src was published in 1980 and the characterization of sites for tyrosine phosphorylation in the transforming protein of Rous sarcoma virus and its normal cellular homologue was published in 1981.
- Vogt PK (September 2012). "Retroviral oncogenes: a historical primer". Nat. Rev. Cancer. 12 (9): 639–48. doi:10.1038/nrc3320. PMC 3428493. PMID 22898541.
- Stehelin D, Fujita DJ, Padgett T, Varmus HE, Bishop JM (1977). "Detection and enumeration of transformation-defective strains of avian sarcoma virus with molecular hybridization". Virology. 76 (2): 675–84. doi:10.1016/0042-6822(77)90250-1. PMID 190771.
- Rudd CE, Trevillyan JM, Dasgupta JD, Wong LL, Schlossman SF (July 1988). "The CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (pp58) from human T lymphocytes". Proc. Natl. Acad. Sci. U.S.A. 85 (14): 5190–4. doi:10.1073/pnas.85.14.5190. PMC 281714. PMID 2455897.
- Czernilofsky AP, Levinson AD, Varmus HE, Bishop JM, Tischer E, Goodman HM (September 1980). "Nucleotide sequence of an avian sarcoma virus oncogene (src) and proposed amino acid sequence for gene product". Nature. 287 (5779): 198–203. doi:10.1038/287198a0. PMID 6253794.
- Smart JE, Oppermann H, Czernilofsky AP, Purchio AF, Erikson RL, Bishop JM (October 1981). "Characterization of sites for tyrosine phosphorylation in the transforming protein of Rous sarcoma virus (pp60v-src) and its normal cellular homologue (pp60c-src)". Proc. Natl. Acad. Sci. U.S.A. 78 (10): 6013–7. doi:10.1073/pnas.78.10.6013. PMC 348967. PMID 6273838.