KRAS (Kirsten rat sarcoma virus) is a gene that provides instructions for making a protein called K-Ras, a part of the RAS/MAPK pathway. The protein relays signals from outside the cell to the cell's nucleus. These signals instruct the cell to grow and divide (proliferate) or to mature and take on specialized functions (differentiate). It is called KRAS because it was first identified as a viral oncogene in the Kirsten RAt Sarcoma virus.[5] The oncogene identified was derived from a cellular genome, so KRAS, when found in a cellular genome, is called a proto-oncogene.
The K-Ras protein is a GTPase, a class of enzymes which convert the nucleotide guanosine triphosphate (GTP) into guanosine diphosphate (GDP). In this way the K-Ras protein acts like a switch that is turned on and off by the GTP and GDP molecules. To transmit signals, it must be turned on by attaching (binding) to a molecule of GTP. The K-Ras protein is turned off (inactivated) when it converts the GTP to GDP. When the protein is bound to GDP, it does not relay signals to the nucleus.
The gene product of KRAS, the K-Ras protein, was first found as a p21 GTPase.[6][7] Like other members of the ras subfamily of GTPases, the K-Ras protein is an early player in many signal transduction pathways. K-Ras is usually tethered to cell membranes because of the presence of an isoprene group on its C-terminus. There are two protein products of the KRAS gene in mammalian cells that result from the use of alternative exon 4 (exon 4A and 4B respectively): K-Ras4A and K-Ras4B. These proteins have different structures in their C-terminal region and use different mechanisms to localize to cellular membranes, including the plasma membrane.[8]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000133703 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030265 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Tsuchida N, Ryder T, Ohtsubo E (September 1982). "Nucleotide sequence of the oncogene encoding the p21 transforming protein of Kirsten murine sarcoma virus". Science. 217 (4563): 937–939. Bibcode:1982Sci...217..937T. doi:10.1126/science.6287573. PMID 6287573.
- ^ Markov K (1979). "[Current state of our knowledge about prostaglandins]". Patologicheskaia Fiziologiia I Eksperimental'naia Terapiia. 76 (5): 3–15. doi:10.1073/pnas.76.10.5355. PMC 413141. PMID 228228.
- ^ Kranenburg O (November 2005). "The KRAS oncogene: past, present, and future". Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 1756 (2): 81–82. doi:10.1016/j.bbcan.2005.10.001. PMID 16269215.
- ^ Welman A, Burger MM, Hagmann J (September 2000). "Structure and function of the C-terminal hypervariable region of K-Ras4B in plasma membrane targetting and transformation". Oncogene. 19 (40): 4582–4591. doi:10.1038/sj.onc.1203818. PMID 11030147. S2CID 20878317.