MEKKS, GCKS, MLKS, PAKS, TAKS, AND TPLS - UPSTREAM REGULATORS OF THE C-JUN AMINO-TERMINAL KINASES

Regulation of the mitogen-activated protein kinase (MAPK) family membe rs - which include the extracellular response kinases (ERKs), p38/HOG1 , and the c-Jun amino-terminal kinases (JNKs)- plays a central role in mediating the effects of diverse stimuli encompassing cytokines, horm ones, growth factors and stresses such as osmotic imbalance, heat shoc k, inhibition of protein synthesis and irradiation. A rapidly increasi ng number of kinases that activate the JNK pathways has been described recently, including the MAPK/ERK kinase kinases, p21-activated kinase s, germinal center kinase, mixed lineage kinases, tumor progression lo cus 2, and TGF-beta-activated kinase. Thus, regulation of the JNK path way provides an interesting example of how many different stimuli can converge into regulating pathways critical for the determination of ce ll fate.