Protein kinases inhibition

GAO Y H and YAMAGUCHI M (2000) Suppressive effect of genistein on rat bone osteoclasts Involvement of protein kinase inhibition and protein tyrosine phosphatase activation. Int J Mol Med 5, 261-7. 

Schaffhauser, H., Cai, Z., Hubalek, F., Macek, T. A., Pohl, J., Murphy, T. J., and Conn, P. J. (2000) cAMP-dependent protein kinase inhibits mGluR2 coupling to G proteins by direct receptor phosphorylation. J. Neurosci. 20, 5663-5670. 

Protein phosphatase I has a phosphorylation site at the C terminus. Phosphorylation at this site by a cyclin-dependent protein kinase inhibits the phosphatase activity. 

In some cases, the domain-binding partner is internal. Phosphorylation of some protein kinases inhibits their activity by favoring the interaction of an SH2 domain with a (P)-Tyr in another domain of the same enzyme. For example, the soluble protein Tyr kinase Src, when phosphorylated on a critical Tyr residue, is rendered inactive as an SH2 domain needed to bind to the substrate protein instead binds to an internal (P)-Tyr... 

Chan, A. Y., Soltys, C. L., Young, M. E., Proud, C. G., and Dyck, J. R. 2004. Activation of AMP-activated protein kinase inhibits protein synthesis associated with hypertrophy in the cardiac myocyte. J Biol Chem 279 32771-32779. 

Kudo, N., Barr, A. J., Barr, R. L., Desai, S., and Lopaschuk, G. D. 1995. High rates of fatty acid oxidation during reperfusion of ischemic hearts are associated with a decrease in malonyl-CoA levels due to an increase in 5 -AMP-activated protein kinase inhibition of acetyl-CoA carboxylase. J Biol Chem 270 17513-17520. 

Gudi, T., Chen, J.C., Casteel, D.E., Seasholtz, T.M., Boss, G.R., and Pilz, R.B. (2002). cGMP-dependent protein kinase inhibits sernm-response element-dependent transcription by inhibiting rho activation and fnnctions. J Biol Chem 277 37382-37393. 

Kwon, T., Kwon, D.Y., Chun, J., Kim, J.H., and Kang, S.S. (2000). Akt protein kinase inhibits Racl-GTP binding through phosphorylation at serine 71 of Racl. J Biol Chem 275 423 28. 

Hendrickson M, Madine M, Dalton S, Gautier J. Phosphorylation of MCM4 by cdc2 protein kinase inhibits the activity of the minichromosome maintenance complex. Proc. Natl. Acad. Sci. U.S.A. 1996 93 12223-12228. 

This study proves to be a successful case study in the field of protein kinase inhibition with ATP competitive compounds (Fig. 20). The hit rate was 36%, and was achieved by screening 103 compounds. 

Bogoyevitch MA, Fairlie DP (2007) A new paradigm for protein kinase inhibition blocking phosphorylation without directly targeting ATP binding. Dmg Discov Today 12 622-633... 

Bates SE,Lee JS,BicksteinB, SpolyarM, Fojo AT. 1993. Differential modulation of P-glycoprotein transport by protein kinase inhibition. Biochemistry 32 9156-64... 

Lazar, D.F., Wiese, R.J., Brady, M.J., Mastick, C.C., Waters, S.B., Yamauchi, K., Pessin, J.E., Cuatrecasas, P. and Saltiel, A.R. Mitogen-activated protein kinase inhibition does not block the stimulation of glucose utilization by insulin. J. Biol. Chem., 1995, 270, 20801-20807. 

The mitochondria have emerged as a central component of the intrinsic apoptotic signaling pathways and are now known to control apoptosis via the release of apopto-genic proteins (Fig.15.8). The apoptotic signals that are channeled through the mitochondrial pathway of apoptosis include various stresses like DNA damage, oxidative stress, UV radiation, protein kinase inhibition, and growth factor deprivation. 

ACC-2 produces malonyl CoA, which inhibits carnitine palmitoyl transferase I, thereby blocking fatty acid entry into the mitochondria. Muscle also contains malonyl CoA decarboxylase, which catalyzes the conversion of malonyl CoA to acetyl CoA and carbon dioxide. Thus, both the synthesis and degradation of malonyl CoA is carefully regulated in muscle cells to balance glucose and fatty acid oxidation. Both allosteric and covalent means of regulation are employed. Citrate activates ACC-2, and phosphorylation of ACC-2 by the adenosine monophosphate (AMP)-activated protein kinase inhibits ACC-2 activity. Phosphorylation of malonyl CoA decarboxylase by the AMP-activated protein kinase activates the enzyme, further enhancing fatty acid oxidation when energy levels are low. 

In Triton skinned smooth muscle, cAMP or the catalytic subunit of cAMP dependent protein kinase inhibits tension development or induces relaxation at submaximal [Ca +] thereby decreasing the Ca -sensitivity of contraction (Kerrick and Hoar 1981, Riiegg et al. 1981, Riiegg and Paul 1982, Sparrow et al. 1984). Inhibition of force was associated with a decrease in LC20 phosphorylation (Riiegg and Pfitzer 1985). The inhibitory... 

Stewart JR, Christman KL, O Brian CA. Effects of resveratrol on the autophosphorylation of phorbol ester- responsive protein kinases inhibition of protein kinase D but not protein kinase C isozyme autophosphorylation. Biochem Pharmacol 2000 60 1355-1359. 

Gani OA, Engh RA. Protein kinase inhibition of clinically important staurosporine analogues. Nat. Prod. Rep. 2010 27(4) 489-498. 

McCombie SW, Bishop RW, Carr D, Dobek E, Kirkup MP, Kirschmeir P, Lin SI, Pet-rin J, Rosinski K, Shankar BB, Wilson O. Indolocarbazoles. 1. Total s)mthesis and protein kinase inhibiting characteristics of compounds related to K-252c. Biooig. Med. Chem. Lett. 1993 3 1537-1542. 

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