Ras and phosphoinositide 3-kinase: partners in development and tumorigenesis - PubMed (original) (raw)
Review
. 2007 Dec 1;6(23):2902-5.
doi: 10.4161/cc.6.23.4996. Epub 2007 Aug 31.
Affiliations
- PMID: 17993782
- DOI: 10.4161/cc.6.23.4996
Review
Ras and phosphoinositide 3-kinase: partners in development and tumorigenesis
Antoine R Ramjaun et al. Cell Cycle. 2007.
Abstract
Much progress has been made in understanding the myriad of intracellular signaling pathways responsible for control of cell physiology. Signalling downstream of receptor tyrosine kinases (RTKs) is probably the most studied signalling mechanism to date and many of the molecular components and corresponding interactions involved have been delineated. Importantly, deregulation of RTK signalling has been implicated in the formation and maintenance of many human tumours. Two of the pivotal molecular components in RTK signalling, Ras and phosphoinositide 3-kinase (PI 3-kinase), have been shown to bind to each other, leading to the activation of PI 3-kinase. However, in addition to this Ras-PI 3-kinase interaction, first described over a decade ago, several other molecular interactions have more recently been described that appear to mediate the same signal. This has brought into question the physiological relevance of the Ras-PI 3-kinase interaction during RTK signalling. Through disruption of the interaction in a mouse model, we have now confirmed that the interaction is highly functional in vivo both during mammalian development and during Ras-induced tumorigenesis. Many questions still remain: in this Perspective, we explore the remaining uncertainties surrounding the role of this signalling mechanism, as well as the future directions that will likely shed further light on its role within cells.
Similar articles
- Nerve growth factor induced stimulation of Ras requires Trk interaction with Shc but does not involve phosphoinositide 3-OH kinase.
Hallberg B, Ashcroft M, Loeb DM, Kaplan DR, Downward J. Hallberg B, et al. Oncogene. 1998 Aug 13;17(6):691-7. doi: 10.1038/sj.onc.1201980. Oncogene. 1998. PMID: 9715270 - Role of RAS in the regulation of PI 3-kinase.
Castellano E, Downward J. Castellano E, et al. Curr Top Microbiol Immunol. 2010;346:143-69. doi: 10.1007/82_2010_56. Curr Top Microbiol Immunol. 2010. PMID: 20563706 Review. - Ras, PI(3)K and mTOR signalling controls tumour cell growth.
Shaw RJ, Cantley LC. Shaw RJ, et al. Nature. 2006 May 25;441(7092):424-30. doi: 10.1038/nature04869. Nature. 2006. PMID: 16724053 Review. - Tyrosine kinase receptor-activated signal transduction pathways which lead to oncogenesis.
Porter AC, Vaillancourt RR. Porter AC, et al. Oncogene. 1998 Sep 17;17(11 Reviews):1343-52. doi: 10.1038/sj.onc.1202171. Oncogene. 1998. PMID: 9779982 Review.
Cited by
- Developmental effects of tobacco smoke exposure during human embryonic stem cell differentiation are mediated through the transforming growth factor-β superfamily member, Nodal.
Liszewski W, Ritner C, Aurigui J, Wong SS, Hussain N, Krueger W, Oncken C, Bernstein HS. Liszewski W, et al. Differentiation. 2012 Apr;83(4):169-78. doi: 10.1016/j.diff.2011.12.005. Epub 2012 Feb 28. Differentiation. 2012. PMID: 22381624 Free PMC article. - The regulation of class IA PI 3-kinases by inter-subunit interactions.
Backer JM. Backer JM. Curr Top Microbiol Immunol. 2010;346:87-114. doi: 10.1007/82_2010_52. Curr Top Microbiol Immunol. 2010. PMID: 20544340 Free PMC article. Review. - Targeting prostate cancer based on signal transduction and cell cycle pathways.
Lee JT, Lehmann BD, Terrian DM, Chappell WH, Stivala F, Libra M, Martelli AM, Steelman LS, McCubrey JA. Lee JT, et al. Cell Cycle. 2008 Jun 15;7(12):1745-62. doi: 10.4161/cc.7.12.6166. Epub 2008 Jun 16. Cell Cycle. 2008. PMID: 18594202 Free PMC article. Review. - PI3K pathway alterations in cancer: variations on a theme.
Yuan TL, Cantley LC. Yuan TL, et al. Oncogene. 2008 Sep 18;27(41):5497-510. doi: 10.1038/onc.2008.245. Oncogene. 2008. PMID: 18794884 Free PMC article. Review. - PDGF/VEGF signaling controls cell size in Drosophila.
Sims D, Duchek P, Baum B. Sims D, et al. Genome Biol. 2009 Feb 12;10(2):R20. doi: 10.1186/gb-2009-10-2-r20. Genome Biol. 2009. PMID: 19216764 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous