Abstract
The c-Jun N-terminal kinase(JNK), which belongs to the mitogen-activated protein kinase family, plays important roles in a broad range of physiological processes. JNK is controlled by two upstream regulators, mitogen-activated protein kinase kinase(MKK)4 and MKK7, which are activated by various MAPKKKs. These two MAPKKs directly phosphorylate specific Tyr and Thr residues located in the activation loop of the JNK protein and activate this kinase in response to environmental stress, pro-inflammatory cytokines or developmental cues. Recent studies, including the analysis with MKK4 and MKK7 knockout mice, have increased our understanding of the physiological roles of JNK signaling in the brain and liver formation, but the precise functions of JNK signaling during early embryogenesis have remained a mystery until relatively recently. Studies employing a range of animal models have now revealed the essential roles of MAPKKs in diverse developmental contexts, including in dorsoventral patterning, convergent extension and somitogenesis. Focusing primarily on extensive work done in zebrafish models, this paper summarizes the functional properties of MKK4 and MKK7 during vertebrate and invertebrate development, and the mechanisms by which these two MAPKKs regulate multiple steps in the formation of the body plan of an organism.
