MAPK, also

Whereas, activation of MAPKKs and MAPKs (also known as extracellular signal-responsive kinases, ERKs), through traw -phosphorylation reactions is fairly well understood, activation of the upstream MAPKKKs, such as the Raf family of protein kinases, is more complicated. There are at least three human Raf kinases Raf-1, Raf-A, and Raf-B. The activation of the Raf kinase is controlled by Ras. This is a central point of control of the whole MAP kinase cascade. 

Several patients have exhibited a clinical picture resembling FHH, but no CaR mutations could be identified. These individuals also exhibited various forms of autoimmunity (e.g., antithyroid antibodies) and harbored anti-CaR antibodies that reduced the high CaQ+ -evoked stimulation of MAPK and PLC in cells transfected with the wild type receptor. Thus both antireceptor antibodies and mutations in the CaR can render the receptor resistant to activation by Caq+, producing a clinical picture of mild, PTH-dependent hypocalciuric hypercalcemia [3]. 

MAPK cascades are composed of three cytoplasmic kinases, the MAPKKK, MAPKK, and MAPK, that are regulated by phosphorylation (Fig. 1) [1, 2]. The MAPKKK, also called MEKK for MEK kinase, is a serine/threonine kinase. Selective activation of MAPKKKs by upstream cellular stimuli results in the phosphorylation of MAPKK, also called MEK for MAP/ERK kinase by the MAPKKK. MAPKKK members are structurally diverse and are differentially regulated by specific upstream stimuli. The MAPKK is phosphorylated by the MAPKKK on two specific serine/ threonine residues in its activation loop. The MAPKK family members are dual specificity kinases capable of phosphorylating critical threonine and tyrosine residues in the activation loop of the MAPKs. MAPKKs have the fewest members in the MAPK signaling module. MAPKs are a family of serine/threonine kinases that upon activation by their respective MAPKKs, are capable of phosphorylating cytoplasmic substrates as well as... 

The cAMP responsive element binding factor (CREB) is also activated by phosphorylation. Depending on the stimuli, CREB is the target of a cAMP dependent protein kinase or of kinases called MAPKs, RSK, and CamKIV. As in AP-1, CREB carries a basic leucine zipper motif (bZDP), which mediates homo dimerization of CREB when bound to the CRE. 

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