The src gene product is a nonreceptor protein kinase called pp60src. This protei

Question

The src gene product is a nonreceptor protein kinase called pp60src. This protein is a tyrosine protein kinase that phosphorylates target proteins at specific tyrosine residues. This tyrosine protein kinase is an integral member of a signal transduction pathway leading to the transition from G2 to M phase. The pp60src protein is phosphorylated by an upstream kinase. The phosphorylation changes the conformation of the protein such that its kinase domain is exposed and is able to then phosphorylate downstream target proteins.

How might a point mutation create a hyperactive form of pp60src (the src gene is a proto-oncogene)?

Explanation / Answer

src gene is a proto-oncogene encoding a tyrosine kinase originally discovered by J. Michael Bishop and Harold E. Varmus, for which they won the 1989 Nobel Prize in Physiology or Medicine. It belongs to a family of non-receptor tyrosine kinases called Src family kinases. The discovery of Src family proteins has been instrumental to the modern understanding of cancer as a disease where normally healthy cellular signalling has gone awry. This gene is similar to the v-src gene of Rous sarcoma virus. This proto-oncogene may play a role in the regulation of embryonic development and cell growth. The protein encoded by this gene is a tyrosine-protein kinase whose activity can be inhibited by phosphorylation by c-SRC kinase. Mutations in this gene could be involved in the malignant progression of colon cancer. Two transcript variants encoding the same protein have been found for this gene Site-directed mutagenesis techniques were used to construct defined point mutations within the src gene of the Prague A strain of Rous sarcoma virus. Bisulfite mutagenesis at a BglI restriction site in the src gene yielded three mutations which contained the same single base change, a guanine-to-adenine transition. The resulting genomes encoded an src protein containing a substitution of threonine for alanine at amino acid position 433. Transfection of chicken cells with mutagenized DNA did not result in cellular transformation even though the cells produced a pp60src. Immune complexes containing mutant pp60src did not phosphorylate immunoglobulin G heavy chain or casein.

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