Src oncogene

Fig. 1. Rous sarcoma virus deletion mutant genome (top) and wild-type genome (bottom). The src oncogene is capable of transforming host cells.

What is the structural distinction between the proteins encoded by c sre and v-sre How does this difference render v-src oncogenic ... 

Jove R, Hanafusa H. 1987. Cell transformation by the viral src oncogene. Annu Rev Cell Biol 3 31-56. 

The peroxynitrite generator SIN-1 (0.5 mM) induced apoptosis both in src oncogene-transformed and non-transformed rat fibroblasts 208 F, indicating that peroxynitrite is no selective apoptosis inducer per se, but that selective apoptosis induction in transformed cells by NO is achieved through selective peroxynitrite generation (Heigold et al. 2002). The interaction of NO with target cell derived superoxide anions represents a novel concept for selective apoptosis induction in transformed cells. Apoptosis induction mediated by NO involves mitochondrial depolarisation and is blocked by Bcl-2 overexpression. 

Flier JS, Mueckler MM, Usher P, Lodish HF. Elevated levels of glucose transport and transporter messenger RNA are induced by ras or src oncogenes. Science 1987 235 1492-1495. 

P. Buckhaults, L. Chen, N. Fregien, M. Pierce, Transcriptional regulation of N-acetylgluco-saminyltransferase V by the src oncogene, J Biol Chem, 1997, 272, 19575-19581. 

Many non-receptor tyrosine kinases have been identified as products of retrovirally encoded oncogenes. Non-receptor tyrosine kinases can be divided into two groups transmembrane and cytosolic families. The c-src tyrosine kinase is the prototype of the cytosolic tyrosine kinases. Regions within these non-receptor tyrosine kinases share homology with the Src kinase, known as Src homology 2 and 3 (SH2 and SH3) domains, and mediate protein-protein interactions between the receptor tyrosine kinases and the intracellular targets (reviewed in Cantley et al., 1991 Pawson and Gish, 1992 Mayer and Baltimore, 1993). 

The importance of FAK is underlined by the finding that cells expressing a constitutively active form survive in suspension even though they are homeless. Here, the protein kinase is active regardless of the failure to make contact with an extracellular matrix. Rescue from apoptosis also occurs when cells express constitutively activated oncogenic forms of Ras or Src and thus activate Plj-kinase and the MAP kinase pathway. Unlike FAK, these not only prevent apoptosis but also promote proliferative signals that result in tumor formation. 

Hunt The other corollary is, have you tried putting other activated oncogenes of the signalling variety (such as ras and src) into these cells to make them independent of the exogenous signalling molecules ... 

Recently, luminacin C2 was isolated in a screen for Src kinase inhibitors. In-vitro experiments suggest that it elicits some of its biological effects via disruption of SH3-mediated association of any number of intracellular proteins with Src. See (a) S. Sharma, C. Oneyama, Y. Yamashita, H. Nakano, K. Sugawara, M. Hamada, N. Kosaka, T. Tamaoki, Oncogene 2001, 20, 2068-2079 (b) C. Oneyama, H. Nakano, S. Sharma, Oncogene 2002, 21, 2037-2050. 

Evidence for the first oncogene was found when certain mutants of RSV failed to transform cells at high temperature but did transform cells at low temperature. The mutant virus replicated well at both temperatures. This means that the virus contained a tem-perature-sensitive mutation in a gene that coded for a sarcoma-producing protein, that is, for v-src. 

T. J. Yeatman, Activation of c-Src by receptor tyrosine kinases in human colon cancer cells with high metastatic potential, Oncogene 15 3083 (1997). 

Andoniou, C. E., et al.. The Cbl proto-oncogene product negatively regulates the Src-family tyrosine kinase Eyn by enhancing its degradation. Mol Cell Biol, 2000, 20(3), 851-67. 

Kim, M., et al., Cbl-c suppresses v-Src-induced transformation through ubiquitin-dependent protein degradation. Oncogene, 2004, 23(9), 1645-55. 

The functions of transmembrane receptors can be modified using adaptor motecules. Sometimes the adaptors bring in substrates to the receptor s enzyme activity, but other times they can bring in the activity itsetf. The best known adaptors have protein structurai domains called SH2 or SH3 domains. These adaptors couple various functions to receptor tyrosine kinases (Fig. 9-4). SH2 and SH3 stands for Src homotogy region 2 and 3 because they were discovered first in the oncogene, Src (see tater). These adapters recognize specific phosphotyrosine residues in the autophosphorylated receptor. Src itsetf is not a receptor, but it is a tyrosine kinase. It has an SH2 and SH3 domain to tink it to the receptor and, when this occurs, it becomes activated as a tyrosine kinase. 

Each cell of the human body carries the potential to become cancerous in the form of its proto-oncogenes. The case of the src gene is far from unique. A great many proto-oncogenes have been discovered some of the best known are myc, myb, ras, fes, fins, fos, and jun (these names derive from the retrovirus in which they were discovered e.g., ras comes from a rat sarcoma virus and fes from a feline sarcoma virus). It follows that each of our cells harbors a number of protooncogenes, each of which may become activated and contribute to the formation of a tumor. 

So far, our story has focused on mutated single proto-oncogenes—for example src or ras—as key entities in the generation of cancer. A little reflection will convince us that the story cannot be that simple. 

Soriano, P., Montgomery, C., Geske, R., and Bradley, A. (1991) Targeted Disruption of the s src Proto-Oncogene Produces Osteopetrosis in Mice. Cell6A, 693 702. 

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