RAF protein-serine/threonine kinases: structure and regulation
- PMID: 20674547
- DOI: 10.1016/j.bbrc.2010.07.092
RAF protein-serine/threonine kinases: structure and regulation
Abstract
A-RAF, B-RAF, and C-RAF are a family of three protein-serine/threonine kinases that participate in the RAS-RAF-MEK-ERK signal transduction cascade. This cascade participates in the regulation of a large variety of processes including apoptosis, cell cycle progression, differentiation, proliferation, and transformation to the cancerous state. RAS mutations occur in 15-30% of all human cancers, and B-RAF mutations occur in 30-60% of melanomas, 30-50% of thyroid cancers, and 5-20% of colorectal cancers. Activation of the RAF kinases requires their interaction with RAS-GTP along with dephosphorylation and also phosphorylation by SRC family protein-tyrosine kinases and other protein-serine/threonine kinases. The formation of unique side-to-side RAF dimers is required for full kinase activity. RAF kinase inhibitors are effective in blocking MEK1/2 and ERK1/2 activation in cells containing the oncogenic B-RAF Val600Glu activating mutation. RAF kinase inhibitors lead to the paradoxical increase in RAF kinase activity in cells containing wild-type B-RAF and wild-type or activated mutant RAS. C-RAF plays a key role in this paradoxical increase in downstream MEK-ERK activation.
Copyright 2010 Elsevier Inc. All rights reserved.
Similar articles
-
Wild-type and mutant B-RAF activate C-RAF through distinct mechanisms involving heterodimerization.Mol Cell. 2005 Dec 22;20(6):963-9. doi: 10.1016/j.molcel.2005.10.022. Mol Cell. 2005. PMID: 16364920
-
Raf: a strategic target for therapeutic development against cancer.J Clin Oncol. 2005 Sep 20;23(27):6771-90. doi: 10.1200/JCO.2005.08.036. J Clin Oncol. 2005. PMID: 16170185 Review.
-
Role of raf proteins in cardiac hypertrophy and cardiomyocyte survival.Trends Cardiovasc Med. 2005 Aug;15(6):225-9. doi: 10.1016/j.tcm.2005.06.008. Trends Cardiovasc Med. 2005. PMID: 16182133 Review.
-
C-Raf inhibits MAPK activation and transformation by B-Raf(V600E).Mol Cell. 2009 Nov 13;36(3):477-86. doi: 10.1016/j.molcel.2009.10.017. Mol Cell. 2009. PMID: 19917255
-
RAF expression in human astrocytic tumors.Int J Mol Med. 2009 Jan;23(1):17-31. Int J Mol Med. 2009. PMID: 19082503
Cited by
-
Diagnostic Value of Conventional Polymerase Chain Reaction for Detecting BRAF V595E Mutation in Liquid and Tissue Specimens of Canine Urothelial and Prostate Carcinomas.Animals (Basel). 2024 Aug 31;14(17):2535. doi: 10.3390/ani14172535. Animals (Basel). 2024. PMID: 39272320 Free PMC article.
-
Development of multitarget agents possessing soluble epoxide hydrolase inhibitory activity.Prostaglandins Other Lipid Mediat. 2019 Feb;140:31-39. doi: 10.1016/j.prostaglandins.2018.12.003. Epub 2018 Dec 26. Prostaglandins Other Lipid Mediat. 2019. PMID: 30593866 Free PMC article. Review.
-
Role of Zinc in Immune System and Anti-Cancer Defense Mechanisms.Nutrients. 2019 Sep 22;11(10):2273. doi: 10.3390/nu11102273. Nutrients. 2019. PMID: 31546724 Free PMC article. Review.
-
Revisiting the Role of B-RAF Kinase as a Therapeutic Target in Melanoma.Curr Med Chem. 2024;31(15):2003-2020. doi: 10.2174/0109298673258495231011065225. Curr Med Chem. 2024. PMID: 37855341
-
Upregulation of MAPK pathway is associated with survival in castrate-resistant prostate cancer.Br J Cancer. 2011 Jun 7;104(12):1920-8. doi: 10.1038/bjc.2011.163. Epub 2011 May 10. Br J Cancer. 2011. PMID: 21559022 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous
