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KRAS




V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog
Available structures: 121p, 1aa9, 1agp, 1bkd, 1clu, 1crp, 1crq, 1crr, 1ctq, 1gnp, 1gnq, 1gnr, 1he8, 1iaq, 1ioz, 1jah, 1jai, 1k8r, 1lf0, 1lf5, 1lfd, 1nvu, 1nvv, 1nvw, 1nvx, 1p2s, 1p2t, 1p2u, 1p2v, 1plj, 1plk, 1pll, 1q21, 1qra, 1rvd, 1wq1, 1xcm, 1xd2, 1xj0, 1zvq, 1zw6, 221p, 2c5l, 2ce2, 2cl0, 2cl6, 2cl7, 2clc, 2cld, 2evw, 2pmx, 2q21, 421p, 521p, 5p21, 621p, 6q21, 721p, 821p
Identifiers
Symbol(s) KRAS; C-K-RAS; K-RAS2A; K-RAS2B; K-RAS4A; K-RAS4B; KI-RAS; KRAS1; KRAS2; NS3; RASK2
External IDs OMIM: 190070 MGI: 96680 Homologene: 37990
RNA expression pattern

More reference expression data

Orthologs
Human Mouse
Entrez 3845 16653
Ensembl ENSG00000133703 ENSMUSG00000030265
Uniprot P01116 O70564
Refseq NM_004985 (mRNA)
NP_004976 (protein) 		NM_021284 (mRNA)
NP_067259 (protein)
Location Chr 12: 25.25 - 25.3 Mb Chr 6: 145.17 - 145.21 Mb
Pubmed search [1] [2]

KRAS is a gene encoding the KRas proto-oncogene. Like other members of the Ras gene family, the KRAS protein is a GTPase and is an early player in many signal transduction pathways and is usually associated with cell membranes due to the presence of an isoprenyl group on its c-terminus.

KRAS acts as a molecular on/off switch, once it is turned on it recruits and activates proteins necessary for the propagation of growth factor and other receptors' signal, such as c-Raf and PI 3-kinase. KRAS binds to GTP in the active state and possesses its intrinsic enymatic activity cleves the terminal phosphate of the nucleotide converting it to GDP. Upon conversion of GTP to GDP, KRAS is turned off. The rate of conversion is usually slow but can be sped up dramatically by an accessory protein of the Guanine nucleotide activating protein (GAP) class, for example RasGAP. In turn KRAS can bind to proteins of the Guanine Nucleotide Exchange Factor (GEF) class, for example SOS1, which forces the release of bound nucleotide. Subsequently, the unbound HRAS is released from the GEF and quickly re-binds available GTP or GDP present in the cytosol. Since GTP is substantially more abundant than GDP, this usually results in HRAS activation.

Other members of the Ras family include: HRAS, RRAS and NRAS. These proteins all are regulated in the same manner and appear to differ largely in their sites of action within the cell.

Contents

Genetic Disease Associated with KRAS

Several germline KRAS mutations have been found to be associated with Noonan syndrome[1] and cardio-facio-cutaneous syndrome[2].

Somatic diseases associated with KRAS

Somatic KRAS mutations are found at high rates in Leukemias, colon cancer[3], pancreatic cancer[4] and lung cancer[5]. KRAS mutation is predictive of response to cetuximab therapy in colorectal cancer[6]. According to this reference whatever the expression of EGFR, KRAS mutation is associated with activation of the Ras/MAPK pathway. KRAS mutations can induce non-response[7] to anti-EGFR monoclonals (panitumumab, cetuximab), or EGFR-TK inhibitors (erlotinib, gefitinib).

References

  1. ^ Schubbert S, Zenker M, Rowe SL, et al (2006). "Germline KRAS mutations cause Noonan syndrome". Nat. Genet. 38 (3): 331–6. doi:10.1038/ng1748. PMID 16474405.
  2. ^ Niihori T, Aoki Y, Narumi Y, et al (2006). "Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome". Nat. Genet. 38 (3): 294–6. doi:10.1038/ng1749. PMID 16474404.
  3. ^ Burmer GC, Loeb LA (1989). "Mutations in the KRAS2 oncogene during progressive stages of human colon carcinoma". Proc. Natl. Acad. Sci. U.S.A. 86 (7): 2403–7. PMID 2648401.
  4. ^ Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M (1988). "Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes". Cell 53 (4): 549–54. PMID 2453289.
  5. ^ Tam IY, Chung LP, Suen WS, et al (2006). "Distinct epidermal growth factor receptor and KRAS mutation patterns in non-small cell lung cancer patients with different tobacco exposure and clinicopathologic features". Clin. Cancer Res. 12 (5): 1647–53. doi:10.1158/1078-0432.CCR-05-1981. PMID 16533793.
  6. ^ Lièvre A, Bachet JB, Le Corre D, et al (2006). "KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer". Cancer Res. 66 (8): 3992–5. doi:10.1158/0008-5472.CAN-06-0191. PMID 16618717.
  7. ^ EGF receptor. Retrieved on 2007-11-05.

Further reading

  • Kahn S, Yamamoto F, Almoguera C, et al. (1987). "The c-K-ras gene and human cancer (review).". Anticancer Res. 7 (4A): 639-52. PMID 3310850.
  • Yamamoto F, Nakano H, Neville C, Perucho M (1985). "Structure and mechanisms of activation of c-K-ras oncogenes in human lung cancer.". Prog. Med. Virol. 32: 101-14. PMID 3895297.
  • Porta M, Ayude D, Alguacil J, Jariod M (2003). "Exploring environmental causes of altered ras effects: fragmentation plus integration?". Mol. Carcinog. 36 (2): 45-52. doi:10.1002/mc.10093. PMID 12557259.
  • Smakman N, Borel Rinkes IH, Voest EE, Kranenburg O (2006). "Control of colorectal metastasis formation by K-Ras.". Biochim. Biophys. Acta 1756 (2): 103-14. doi:10.1016/j.bbcan.2005.07.001. PMID 16098678.
  • Castagnola P, Giaretti W (2006). "Mutant KRAS, chromosomal instability and prognosis in colorectal cancer.". Biochim. Biophys. Acta 1756 (2): 115-25. doi:10.1016/j.bbcan.2005.06.003. PMID 16112461.
  • Deramaudt T, Rustgi AK (2006). "Mutant KRAS in the initiation of pancreatic cancer.". Biochim. Biophys. Acta 1756 (2): 97-101. doi:10.1016/j.bbcan.2005.08.003. PMID 16169155.
  • Pretlow TP, Pretlow TG (2006). "Mutant KRAS in aberrant crypt foci (ACF): initiation of colorectal cancer?". Biochim. Biophys. Acta 1756 (2): 83-96. doi:10.1016/j.bbcan.2005.06.002. PMID 16219426.
  • Su YH, Wang M, Aiamkitsumrit B, et al. (2007). "Detection of a K-ras mutation in urine of patients with colorectal cancer.". Cancer biomarkers : section A of Disease markers 1 (2-3): 177-82. PMID 17192038.

External links

  • MeSH KRAS2+protein,+human


 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "KRAS". A list of authors is available in Wikipedia.
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