Src gene

Normal cells also were found to contain src-like genes when their DNA was hybridized with labeled nucleic acid probes from the v-src gene. As with other cellular genes, the c-onc genes were interrupted with introns. v-Onc genes lack introns. Consequently, in the distant past c-onc genes must have been transferred to the retroviruses. If the transfer had been from the virus to the cell, c-onc genes probably would not contain introns. 

Vinculin is one of a number of proteins that bind the actin network to the plasma membrane. It is a 130-kDa protein that is phosphorylated at a tyrosine residue by a kinase that is controlled by the src gene. Vinculin function is Ca2+-dependent, and it is found in close association with a-actinin. 

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. 

The second type of point mutation results in the replacement of one amino acid with another. Such mutations will have more or less of an effect depending on which amino acid is changed. Obviously, if a critical amino acid is replaced by one that is unable to provide the same function, the protein will lose some or all of its activity. Mutations within that Ras and Src genes are two examples in which point mutations lead to disease. In the case of the Ras protein, substitution of a single amino acid, most commonly at either position 12 or 61, is associated with the occurrence of several human tumors. In the case of the Src protein, a point mutation that occurs in a tyrosine residue leads to the constitutive activation of the protein and is associated once again with several types of tumors. 

Some representatives of the retroviruses cause tumors in animals such as mice or chickens. The discovery of oncogenes initiated from the src gene of Rous sarcoma virus, which could be identified as the tumor causing principle of this retrovirus. The src gene codes for the Src tyrosine kinase (see 8.3). The gene sections of retroviruses responsible for tumor formation were designated oncogenes. 

FIGURE 26-31 Rous sarcoma vims genome. The src gene encodes a tyrosine-specific protein kinase, one of a class of enzymes known to function in systems that affect cell division, cell-cell interactions, and intercellular communication (Chapter 12). The same gene is found in... 

Retroviral-Associated Oncogenes That Are Involved in Growth Regulation The src Gene Product The sis Gene Product The erbB Gene Product The ras Gene Product... 

Michael Bishop and Harold Varmus discovered the c-src gene in uninfected cells, which is homologous to the v-src gene in the Rous sarcoma virus. 

Behrens, J., Vakaet, L., Friis, R., Winterhager, E., Van Roy, F., et al. 1993. Loss of epithelial differentiation and gain of invasiveness correlates with tyrosine phosphorylation of the E-cadherin/beta-catenin complex in cehs transformed with a temperature-sensitive v-SRC gene. J. Cell Biol. 120 757-766. 

The SH2 domain is a conserved sequence in a viral tyrosine kinase responsible for transforming fibroblasts into neoplastic sarcoma cells (the viral src gene, v-src, see sect. 10.2.1. for the normal cell counterpart, c-src). SHI is a tyrosine kinase domain SH2 is the domain that binds to phosphotyrosine residues and SH3 is a v-src domain that binds to proline-rich sequences in proteins. SH2 and SH3 domains are found in many proteins involved in signal transduction. 

For example, Rous sarcoma virus is a retrovirus that causes sarcoma (a cancer of tissues of mesodermal origin such as muscle or connective tissue) in chickens. In addition to the genes necessary for viral replication, this virus carries a gene termed v-sre. The v-src gene is an oncogene it leads to the transformation of susceptible cell types— that is, the generation of... 

Sequence analysis of the src gene from viruses and cells revealed small differences between the two. Thus, v-src, refers to the viral form of the gene and c-src to the cellular form. Analysis of many other tumor vimses yielded more than two dozen additional oncogenes. The corresponding proto-oncogenes encode a variety of proteins involved in cell signaling, some of which are identified in Table 23.7. 

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