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The AGC kinase group defines the subgroup of Ser/Thr protein kinases named after 3 representative families, the cAMP-dependent protein kinase (PKA), the cGMP-dependent protein kinase (PKG) and the protein kinase C (PKC) families. The AGC family contains more than 60 human protein kinases which have been highly conserved throughout eukaryotic evolution and can be classified into 14 subfamilies. A unique feature of AGC kinases is the presence of a C-terminal segment containing a hydrophobic motif within the catalytic domain whereas the selectivity and specificity in the regulation of AGC kinases is predominantly derived from the regions located N- and C-terminal to the catalytic core.
The calcium/calmodulin-dependent kinases (CaMKs) are a subfamily of serine/threonine kinases that translate and coordinate an increase of intracellular Ca2+ concentration into cellular responses via phosphorylation. The activity of this kinases is regulated primary by the Ca2+ receptor protein calmodulin (CaM). The multifunctional CAMK family is comprised of CAMKI, CAMKIV and CAMKK - all part of the so called Ca-calmodulin-dependent protein kinase cascade and the CAMKII subfamily. The dedicated kinases (which are dedicated to a single substrate) includes e.g. phosphorylase kinase, myosin light chain kinase (MLCK), and eukaryotic elongation factor-2 kinase.
The name CMGC family of kinases corresponds to the cyclin-dependent kinases (CDK), mitogen-activated protein kinases (MAPK), glycogen synthase kinase (GSK3) and CDC-like kinase (CLK) group of protein kinases. CMGC kinases display unique features such as the “CMGD arginine” which is located near the substrate phosphorylation site in the activation loop and the so-called “CMGC-insert region” in the C-terminal lobe serving as specific docking region. The kinases are involved in cell-cycle regulation and signaling, cell communication and cell growth.
The protein kinase CK1 (formerly called Casein Kinase 1) group represents a small group of of serine/threonine protein kinases involved in many diverse and important cellular functions, such as regulation of membrane transport, cell division, DNA repair, and nuclear localization.
The STE group includes homologs of the yeast sterile kinases sterile 7, sterile 11, and sterile 20, which sequentially activate each other and MAPK members. Ste20 kinases (MAP4K) act on Ste11 kinases (MAP3K), which phosphorylates and activates dual specificity MAPK kinase (Ste7)(MAP2K, MEK, MKKs) member upstream of MAPKs of the CMGC group. The Ste20 group kinases are further divided into the p21-activated kinase (PAK) and germinal center kinase (GCK) families.
The protein tyrosine kinase group can be divided into two main groups: cytosolic tyrosine kinases (CTKs) or non-receptor tyrosine kinases (e.g. Src, JAK, Abl) and receptor tyrosine kinases (RTK). Receptor tyrosine kinases such as EGFR, VEGFR, FLT3 are transmembrane proteins that are activated by the binding of an extracellular ligand that transduces the signal to the cytoplasm by phosphorylating tyrosine residues on the receptors themselves (autophosphorylation) and on downstream signaling proteins. Since tyrosine kinases regulate many key processes including cell growth and survival a dysregulation has been found in the development and progression of a wide range of cancers.
The Tyr kinase-like (TKL) group is closely related to the Tyrosine kinase group (TK) although the kinase group comprises predominantly serine/threonine kinases. Prominent mebers are the the Raf family kinases, acting as important components of the MAP kinase pathway, and TGF beta receptors involved in in many cellular processes such as cell growth, cell differentiation and apoptosis.
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