V-Src

Last updated
Tyrosine-protein kinase transforming protein Src
Identifiers
Organism Rous sarcoma virus
Symbolv-src
Alt. symbolspp60v-src
Entrez 1491925
RefSeq (Prot) NP_056888.1
UniProt P00526
Other data
EC number 2.7.10.2
Chromosome viral: 0.01 - 0.01 Mb
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Structures Swiss-model
Domains InterPro

v-Src is a gene found in Rous sarcoma virus (RSV) that encodes a tyrosine kinase that causes a type of cancer in chickens.

Contents

The src gene is oncogenic as it triggers uncontrolled growth in abnormal host cells. It was the first retroviral oncogene to be discovered. [1] The src gene was taken up by RSV and incorporated into its genome [2] conferring it with the advantage of being able to stimulate uncontrolled mitosis of host cells, providing abundant cells for fresh infection.

The src gene is not essential for RSV proliferation but it greatly increases virulence when present.

Discovery

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).

Function

Further research done later on by others showed that RSV was a type of retrovirus. It was found that the v-Src gene in RSV is required for the formation of cancer. [3]

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. [4] 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 [5] 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. [6]

See also

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References

  1. ↑ Vogt PK (September 2012). "Retroviral oncogenes: a historical primer". Nat. Rev. Cancer. 12 (9): 639–48. doi:10.1038/nrc3320. PMC   3428493 . PMID   22898541.
  2. ↑ Swanstrom, R; Parker, R C; Varmus, H E; Bishop, J M (May 1983). "Transduction of a cellular oncogene: the genesis of Rous sarcoma virus". Proceedings of the National Academy of Sciences. 80 (9): 2519–2523. doi: 10.1073/pnas.80.9.2519 . PMID   6302692.
  3. ↑ 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.
  4. ↑ 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. Bibcode:1988PNAS...85.5190R. doi: 10.1073/pnas.85.14.5190 . PMC   281714 . PMID   2455897.
  5. ↑ 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. Bibcode:1980Natur.287..198C. doi:10.1038/287198a0. PMID   6253794. S2CID   4231060.
  6. ↑ 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. Bibcode:1981PNAS...78.6013S. doi: 10.1073/pnas.78.10.6013 . PMC   348967 . PMID   6273838.
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