BRAF mutations in human cancer: Biologic and therapeutic implications Book Section
| Authors: | Nissan, M. H.; Solit, D. B. |
| Editors: | Gelmann, E. P.; Sawyers, C. L.; Rauscher, F. J. 3rd |
| Article/Chapter Title: | BRAF mutations in human cancer: Biologic and therapeutic implications |
| Abstract: | Introduction The Mitogen-Activated Protein Kinase (MAPK or ERK) pathway is a central regulator of cellular proliferation and is frequently activated in human tumors. This pathway consists of the RAF, MEK (mitogen-activated protein kinase (MAPK) kinase) and ERK (extra-cellular signal-regulated kinase) kinases (see Figure 22.1). In normal cells, the RAS (K-, N-, and HRAS) small GTPase proteins activate the RAF kinases (ARAF, BRAF, and CRAF/RAF1) by regulating their cellular localization and homo- and heterodimerization (1). Recruitment of RAF to the plasma membrane by activated RAS induces an “open” conformation, which facilitates its phosphorylation and resulting kinase activation (2). Activation of RAF initiates a series of phosphorylation events, including the phosphorylation of the MEK1 and MEK2, and ERK1 and ERK2 kinases. Phosphorylated ERK in turn regulates several cellular processes such as cell-cycle progression and survival through phosphorylation of nuclear transcription factors and cytosolic proteins (3–8). The ERK pathway operates as a negative feedback loop in which activation of the pathway is balanced by feedback regulatory elements including the dual-specificity phosphatases (DUSPs) and the Sprouty family proteins, the expression of which are ERK dependent (9,10). ERK pathway activity is also regulated by cross-talk with parallel signaling pathways such as the PI3K/AKT pathway and by scaffold proteins such as 14-3-3 that regulate RAF subcellular localization and stability (11). © Cambridge University Press 2014. |
| Book Title: | Molecular Oncology: Causes of Cancer and Targets for Treatment |
| ISBN: | 978-0-521-87662-9 |
| Publisher: | Cambridge University Press |
| Publication Place: | Cambridge, UK |
| Date Published: | 2014-01-01 |
| Start Page: | 272 |
| End Page: | 277 |
| Language: | English |
| DOI: | 10.1017/cbo9781139046947.023 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Book Chapter: 22 -- Molecular Oncology: Causes of Cancer and Targets for Treatment -- 9781139046947 (eISBN); 9780521876629 (ISBN) -- Export Date: 3 February 2016 -- Source: Scopus |
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