The CMGC Group
The CMGC (including cyclin-dependent kinases (CDKs), mitogen-activated protein kinases (MAP kinases), glycogen synthase kinases (GSK) and CDK-like kinases) are an essential and typically large group of kinases found in all eukaryotes. CDKs regulate the progression through the different phases of the cell cycle in association with their activating partners cyclins. Tumour progression is frequently associated with genetic or epigenetic alterations in CDKs (or cyclins), which help sustain proliferation with independence from external mitogenic or antimitogenic signals.
MAP kinases were discovered in the late 1980s and, together with their immediate upstream phosphorylating kinases, are among the most highly studied signal transduction molecules. MAP kinases play a key role in the regulation of many cellular processes and MAP kinase cascades participate extensively in the control of cell fate deicisions such as proliferation, differentiation and death across all eukaryotic phyla and in all tissues of metazoans. Three major groups of MAP kinases have been identified in mammals: extracellular signal-related kinase (ERK), which is typically stimulated by growth related signals, the JNK and p38 MAP kinase cascades however, are activated by a variety of stress stimuli. ERK is involved in long-lasting neuronal plasticity, including long-term potentiation and memory consolidation. With the abundant expression of MAP kinases in the central nervous system, an understanding of the role of these molecules in psychiatric disorders is beggining to emerge.
GSK3, initially described as a key enzyme involved in glycogen metabolism, is now known to regulate a diverse array of functions. GSK3 is a well-established component of the Wnt pathway, which is essential for establishing the entire body pattern during embryonic development. The substrate specificity of GSK3 is unusual in that the efficient phosphorylation of many of its substrates requires the presence of another phosphorylated residue optimally located four amino acid residues C-terminal to the site of GSK3 phosphorylation.
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