Protein Ser/Thr kinases

I. Ser/Thr protein kinases A. Cyclic nncleotide-dependent cAMP-dependent (PKA) —R(R/K)X(S /T ) — cAMP... 

One of the downstream elements of the signal transduction pathway, MAPKK (or, MEK) is phosphorylated by a Ser/Thr protein kinase, known as Raf, and phosphorylated MAPKK then catalyzes phosphoryl transfer to MAP kinase. The following is a recent review on the molecular and physical properties of this phosphotransferase (or, MAP kinase kinase). 

The use of the 6-amino group and N1 nitrogen of the purine base to model the pharmacophore, as seen with staurosporine, is not possible in two other adenine-type inhibitors. Both isopentenyl adenine, a nonspecific inhibitor of protein kinases, and olomoucin, a more specific inhibitor of Ser/Thr protein kinases, are modified only at the 6-amino group position. Thus, bidentate hydrogen-bond formation as seen in the ATP purine base is not possible. Furthermore, there are inhibitors that do not contain the chemical structure of adenine, for example des-chloro-flavopyridol, a potent inhibitor of cdc-2 cell cycle kinase. 

Under the electron microscope titin appears as a flexible beaded string 4 nm in diameter. Most of the molecule is made up of repetitive domains of two types. In human cardiac titin there are 132 folded domains that resemble type III fibronectin repeats and 112 immunoglobulin-like domains.98 In a "PEVK region," between residues 163 and 2174, 70% of the residues are Pro, Glu, Val, or Lys. The titin molecule may be organized as polyproline helices in this elastic region.1023 At the C terminus of titin 800 residues, including a Ser / Thr protein kinase domain, are found within the M-line. 

The R proteins, which act as receptors for Avr, and other elicitor proteins, are usually leucine-rich-repeat proteins with a characteristic nucleotide binding site attached (NB-LRR proteins).534,537 Like other cell surface receptors they participate in signaling and utilize both ion channels and Ser/Thr protein kinases.538 The Arabidopsis genome contains 150 sequences that may represent NB-LRR receptors.530... 

The role of targeting subunits was first recognized in the case of protein kinase C, as it became clear that isotbrms of protein kinase C and their substrates have different subcellular locations, raising the question of how the enzymes find their substrates. PKCs are membrane-attached Ser/Thr protein kinases. They were discovered by... 

Biondi, R.M. and Nebreda, A.R. (2003) Signalling specificity of Ser/Thr protein kinases through docking site-mediated interactions. Biochem.J.,... 

Mitogen-activated protein (MAP) kinase is one of several kinases that play a pivotal role in the transduction of extracellular mitogenic signals to the nucleus (Rossomando et al., 1989 Boulton et al., 1990). MAP kinase is Ser/Thr protein kinase that is fully activated by dual phosphorylation at Thr and Tyr residues (Anderson et al., 1990) and has been shown to activate nuclear transcription factors and stimulate cell growth and proliferation. In cultured HeLa cells (Chen et al.,... 

Inhibition of EGF-R tyrosine kinase by hypericin 1 was shown to be irreversible, non-competitive and time as well as temperature dependent. The IC50 increased from 0.75 pM in the dark to 44 nM with light illumination for 30 min. This effect was presumably due to a type I photosensitization mechanism since exclusion of oxygen did not alter the inhibition curve. Some Ser/Thr protein kinases (e.g., protein kinase A, casein kinase 1 and 2) and the enzyme 5 -nucleotidase were not inhibited even at concentrations > 100 pM [144]. However, the same authors recently reported that hypericin 1 in addition to protein kinase C also caused the light-dependent inhibition of certain other Ser/Thr kinases (e.g. protein kinase CK-2, mitogen-activated kinase) and the insulin receptor tyrosine kinase, while it was ineffective towards the cytosolic tyrosine kinases Lyn, Fgr, TPK-IIB and CSK. These results suggest that distantly related protein kinases could still share common reactive domains for the interaction with hypericin 1 [156]. In contrast to the above mentioned studies, Richter and Davies [157] observed no inhibition of EGF-induced tyrosine phosphorylation of the EGF-R in HN5 squamous carcinoma... 

Ikebe M, Brozovich FV (1996) Protein kinase C increases force and slows relaxation in smooth muscle evidence for regulation of the myosin light chain phosphatase. Biochem Biophys Res Commun 225 370-376 Ikebe M, Reardon S (1989) Location of the inhibitory region of smooth muscle myosin light chain kinase. J. Biol Chem 264 6967-6971 Ishizaki T, Maekawa M, Fujisawa K, Okawa K, Iwamatsu A, Fujita A, Watanabe N, Saito Y, Kakizuka A, Morri N, Narumiya S. (1996) The small GTP-binding protein Rho binds to and activates a 160 kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase. EMBO J 15 1885-1893... 

Feng, B., Chen, Y.R, Zhao, C. et al. 2006. Isolation of a novel Ser/Thr protein kinase gene from oligochito-san-induced tobacco and its role in resistance against tobacco mosaic virus. Plant Physiol. Biochem. 44 596-603. 

Phosphomannose addition to yeast mannan, which occurs at a late stage in cell growth and in response to high osmolarity, is positively regulated by a putative Ser/Thr protein kinase encoded by the stress-responsive MNN4 gene [59]. 

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