Reviews–A Peer Reviewed Forum
MAP3Ks as central regulators of cell fate during development
Article first published online: 14 OCT 2008
Copyright © 2008 Wiley-Liss, Inc.
Volume 237, Issue 11, pages 3102–3114, November 2008
How to Cite
Craig, E. A., Stevens, M. V., Vaillancourt, R. R. and Camenisch, T. D. (2008), MAP3Ks as central regulators of cell fate during development. Dev. Dyn., 237: 3102–3114. doi: 10.1002/dvdy.21750
- Issue published online: 21 OCT 2008
- Article first published online: 14 OCT 2008
- Manuscript Accepted: 18 AUG 2008
- MAP3 Kinase;
- mouse knockout;
The cytoplasmic serine/threonine kinases transduce extracellular signals into regulatory events that impact cellular responses. The induction of one kinase triggers the activation of several downstream kinases, leading to the regulation of transcription factors to affect gene function. This arrangement allows for the kinase cascade to be amplified, and integrated according to the cellular context. An upstream mitogen or growth factor signal initiates a module of three kinases: a mitogen-activated protein (MAP) kinase kinase kinase (MAPKKK; e.g., Raf) that phosphorylates and activates a MAP kinase kinase (MAPKK; e.g., MEK) and finally activation of MAP kinase (MAPK; e.g., ERK). Thus, this MAP3K-MAP2K-MAPK module represents critical effectors that regulate extracellular stimuli into cellular responses, such as differentiation, proliferation, and apoptosis all of which function during development. There are 21 characterized MAP3Ks that activate known MAP2Ks, and they function in many aspects of developmental biology. This review summarizes known transduction routes linked to each MAP3K and highlights mouse models that provide clues to their physiological functions. This perspective reveals that some of these MAP3K effectors may have redundant functions, and also serve as unique nexus depending on the context of the signaling pathway. Developmental Dynamics 237:3102–3114, 2008. © 2008 Wiley-Liss, Inc.