Protein serine/threonine kinase

Serine/threonine protein kinase phosphorelay modules... 

S6K1 (also known as p70S6 kinase) is a serine/ threonine protein kinase which is involved in the regulation of translation by phosphorylating the 40S ribosomal protein S6. Insulin and several growth factors activate the kinase by phosphorylation in a PI 3-kinase dependent and rapamycin-sensitive manner. Phosphorylation of S6 protein leads to the translation of mRNA with a characteristic 5 polypyrimidine sequence motif. 

HAGIWARA M, INOUE s, TANAKA T, NUNOKI K, ITO M and HiDAKA H (1988) Differen-tial effects of flavonoids as inhibitors of tyrosine protein kinases and serine/threonine protein kinases Biochemical Pharmacology 37, 2987-92. 

Cytoplasmic serine/threonine protein kinases catalyze the transfer of phosphate groups to serine and threonine residues of target proteins. Serine/threonine kinases have been recognized as the products of protooncogenes (e.g., c-mos, c-raj) or as kinases intimately involved with the regulation of serine/threonine kinase activity by cAMP. Some of these kinases specifically phosphorylate cellular structural proteins, such as histone, laminins, etc. Others phosphorylate still more kinases, resulting in either the activation or deactivation of downstream protein kinases. Specific examples in which serine/threonine kinases elicit specific cellular responses are discussed in this chapter. 

Crews, C. M., Alessandrini, A. A., and Erikson, R. L. (1991). Mouse Erk-1 gene product is a serine/threonine protein kinase that has the potential to phosphorylate tyrosine. Proc. Natl. Acad. Sci. USA 88 8845-8849. 

Rapp, U. R. (1991). Role of Raf-1 serine/threonine protein kinase in growth factor signal transduction. Oncogene 6 495-500. 

Rossomando, A. J., Saanghcra, J. S., Marsden, L. A., Weber, M. J., Pelech, S. L., and Sturgill, T. W. (1991). Biochemical characterization of a family of serine/threonine protein kinases regulated by tyrosine and serine/threonine phosphorylation. J. Biol. Chem. 266 20270-20275. 

Protein kinase B, or Akt, was discovered as the product of an oncogene of the acutely transforming retrovirus AKT8, causing T-cell lymphomas in mice. It encodes a fusion product of a cellular serine/threonine protein kinase and the viral structural protein Gag. This kinase is similar to both protein kinase Ce (PKCe 73% identity to the catalytic domain) and protein kinase A (PKA 68%). It differs from other protein kinases in that it contains a pleckstrin homology (PH) domain, which allows it to bind to polyphosphoinositide head groups (and also to G-protein fly subunits). To date, three subtypes have been identified a, (3, and y, all of which show a broad tissue distribution. It... 

Arden, S.R., Smith, A.M., Booth, M.J., Tweedie, S., Gounaris, K. and Selkirk, M.E. (1997) Identification of serine/threonine protein kinases secreted by Trichinella spiralis infective larvae. Molecular and Biochemical Parasitology 90, 111-119. 

Identification of serine/threonine protein kinases secreted by Trichinella spiralis infective larvae. Molecular and Biochemical Parasitology 90, 111-119. 

STKc Serine/threonine protein kinases, cytalytic domain E(MFP)B 112(112) 256(260) 1A9U... 

Fig. 6. Distribution of the most common folds in selected bacterial, archaeal, and eukaryotic proteomes. The vertical axis shows the fraction of all predicted folds in the respective proteome. Fold name abbreviations FAD/NAD, FAD/NAD(P)-binding Rossman-like domains TIM, TIM-barrel domains SAM-MTR, S-adenosylmethionine-dependent methyltransferases PK, serine-threonine protein kinases PP-Loop, ATP pyrophosphatases. mge, Mycoplasma genitalium rpr, Rickettsiaprowazekii hh x, Borrelia burgdorferi ctr, Chlamydia trachomatis hpy, Helicobacter pylori tma, Thermotoga maritima ssp, Synechocystis sp. mtu, Mycobacterium tuberculosis eco, Escherichia coli mja, Methanococcus jannaschii pho, Pyrococcus horikoshii see, Saccharomyces cerevisiae, cel, Caenorhabditis elegans.

The switch in the action of the enzyme between its kinase and phosphatase activities is brought about by phosphorylation mediated by the serine/threonine protein kinase A (PKA), the same cAMP dependent enzyme which plays a role in the control of glycogen metabolism. In its kinase form, PFK-2 is dephosphorylated but phosphorylated in the phosphatase form. 

Inositol triphosphate (IP3), which raises intracellular Ca + concentrations by inducing its release from intracellular stores. This Ca +, in turn, activates a cytoplasmic serine/ threonine protein kinase. 

The TGF- Ss exert their biological actions by binding to specific receptors, of which there are three types (I, II and III). All are transmembrane glycoproteins. All three TGF-)Ss bind to all three receptor types, although they bind with higher affinity to types I and II receptors (53 kDa and 65 kDa, respectively). The intracellular domains of the type I and II receptors display endogenous serine/threonine protein kinase activity. 

Bourouis M, Moore P, Ruel L, Grau Y, Heitzler P, Simpson P 1990 An early embryonic product of the gene shaggy encodes a serine/threonine protein kinase related to the CDC28/cdc2+ subfamily. EMBO J 9 2877-2884... 

Ro-4584820, a cyclin-dependent kinase (CDK) inhibitor, is in Phase 1 of clinical evaluation. CDKs are a family of serine/threonine protein kinases that play key roles in the normal growth and life cycle of eukaryotic cells. 

The serine/threonine protein kinases transfer a phosphate from ATP to a serine or threonine residue in the target protein. This class of enzymes are generally associated with cytoplasmic signaling events. 

---