v-Src is a

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

found in Rous sarcoma virus (RSV) that encodes a

tyrosine kinase A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions. Tyrosine kinases belong to a larger cla ...

that causes a type of cancer in chickens. The

src gene Tyrosine-protein kinase CSK also known as C-terminal Src kinase is an enzyme that, in humans, is encoded by the CSK gene. This enzyme phosphorylates tyrosine residues located in the C-terminal end of Src-family kinases (SFKs) including SRC, HCK, ...

oncogenic Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abno ...

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 In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...

conferring it with the advantage of being able to stimulate uncontrolled

mitosis In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...

of host cells, providing abundant cells for fresh

infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...

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

virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ca ...

when present.

Discovery

Francis Peyton Rous Francis Peyton Rous () (October 5, 1879 – February 16, 1970) was an American pathologist at the Rockefeller University known for his works in oncoviruses, blood transfusion and physiology of digestion. A medical graduate from the Johns Hopki ...

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 A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. Once inside the host cell's cytoplasm, the virus uses its own reverse transcriptase ...

. It was found that the ''v-Src'' gene in RSV is required for the formation of cancer. 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 Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, ...

-dependent signals central to

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...

movement and proliferation. Hallmarks of v-Src induced transformation are rounding of the cell and the formation of actin rich

podosome Podosomes are conical, actin-rich structures found on the outer surface of the plasma membrane of animal cells. Their size ranges from approximately 0.5 µm to 2.0 µm in diameter. While usually situated on the periphery of the cellular ...

s 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 The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...

inhibitory phosphorylation site (tyrosine-527), and is therefore constitutively active as opposed to normal Src (

c-Src Proto-oncogene tyrosine-protein kinase Src, also known as proto-oncogene c-Src, or simply c-Src (cellular Src; pronounced "sarc", as it is short for sarcoma), is a non-receptor tyrosine kinase protein that in humans is encoded by the ''SRC'' gene ...

) 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 An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

whereas c-Src is a

proto-oncogene An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

. 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.

References

{{Reflist, 35em Oncogenes

Discovery

Function

See also

References