Kinase catalytic

Tyrosine phosphorylated IRS interacts with and activates PI 3-kinase [3]. Binding takes place via the SRC homology 2 (SH2) domain of the PI 3-kinase regulatory subunit. The resulting complex consisting of INSR, IRS, and PI 3-kinase facilitates interaction of the activated PI 3-kinase catalytic subunit with the phospholipid substrates in the plasma membrane. Generation of PI 3-phosphates in the plasma membrane reemits phospholipid dependent kinases (PDKl and PDK2) which subsequently phosphorylate and activate the serine/threonine kinase Akt (synonym protein... 

The partial backbone assignment of the catalytic domain of protein kinase A (PKA) using a combination of NMR techniques was reported in 2004 [51]. This represented the first reported NMR assignment of any protein kinase catalytic domain. Backbone resonance assignment of the 42kDa protein was achieved using a combination of triple-labelled ( H, N)... 

All RTKs contain between one and three tyrosines in the kinase activation loop, which is composed of subdomains VII and VIII of the protein kinase catalytic core. Phosphorylation of these tyrosines has been shown to be critical for stimulation of catalytic activity and biological function for a number of RTKs, including insulin receptor, FGF receptor, VEGF receptor, PDGF receptor, Met (hepatocyte growth factor receptor), and TrkA (NGF receptor). A major exception is the EGF receptor, for which autophosphorylation of a conserved tyrosine in the activation loop does not seem to be involved in signaling. Substitution of tyrosine with phenylalanine has no effect on RTK activity or downstream signals. 

The cytoplasmic domain primarily consists of the catalytic domain and various autophosphorylation sites that regulate catalytic function and serve as docking sites for SH2 do main-containing proteins. The protein kinase catalytic domains of RPTKs are highly conserved and similar in structure to those of the NRPTK (see above). 

DAGKc Di acyl glycerol kinase catalytic domain (presumed) E(MFP)B 2(2) 9(9) ... 

PI3Kc Phosphoinositide 3-kinase, catalytic domain E(MFP) 8(8) 9(9) 1QMM... 

FI/F2/F3, triad of RING-finger-like domains F, F-box domain USP, deubiquitinase catalytic domain OTU, a particular class of cystein protease domains RVP, retroviral protease domain DBA, ubiquitin-associated domain Pkinase, protein kinase catalytic domain. 

Selected entries from Methods in Enzymology [vol, page(s)] General Protein kinase classification, 200, 3 protein kinase catalytic domain sequence database identification of conserved features of primary structure and classification of family members,... 

Phosphorylation. To study regulation of enzyme activity, fractions were preincubated with 150 //M ATP, 5 U protein kinase catalytic subunit from bovine heart, 5 mM MgCl2, 60 mM dithiothreitol, 120 //M ATP, 5-80 fig protein depending on source and 50 mM Tris-HCl, pH 8. Samples were held 5 min at 35°C and assayed. 

Hartley, K. O., Gell, D., Smith, G. C., et al., DNA-dependent protein kinase catalytic subunit A relative of phosphatidylinositol 3-kinase and the ataxia telangiectasia gene product. Cell 82, 849-856 (1995). 

Recent work has now shown the conformational diversity of inhibitors binding in the interdomain ATP-binding cleft [26]. Although the residues of the protein kinase catalytic core that form the bidentate donor-acceptor bond with inhibitors are identical throughout different structures, the residues of the inhibitors vary greatly. All inhibitors use this common bidentate bond yet the specificity lies in several other bonds formed between the inhibitor and specific regions of the individual protein kinases. Furthermore, it is difficult to model... 

P.W. Cooper, J.A. Hoekstra, M.F pllOd, a novel phosphatidylinositol 3-kinase catalytic subunit that associates with p85 and is expressed predominantly in leukocytes. J. Biol. Chem., 272, 19236-19241 (1997)... 

Hanks SK, Hunter T (1995) Protein kinases 6. The eukaryotic protein kinase superfamily kinase (catalytic) domain structure and classification. FASEB J 9 576-596... 

Relaxation follows the drop in cytosolic calcium below the activation threshold, which initiates release of calcium from calmodulin, whereupon calmodulin dissociates from the kinase catalytic subunit. This results in loss of myosin light chain kinase activity. Under these conditions, the dephosphorylation of myosin light chains will be the predominant reaction. Consequently, actin and myosin will no longer interact and the muscle relaxes. 

Oka A, Takashima S, Abe M, Araki R, Takeshita K. 2000. Expression of DNA-dependent protein kinase catalytic subunit and Ku80 in developing human brains Implications of DNA-repair in neurogenesis. Neurosci Lett 292 167-170. Okabe S. 2007. Molecular anatomy of the postsynaptic density. Mol Cell Neurosci 34 503-518. 

PI 3-kinases Catalytic subunit Regulatory subunit Substrates... 

Langer T, et al. NMR backbone assignment of a protein kinase catalytic domain by a combination of several approaches application to the catalytic subunit of cAMP-dependent protein kinase. ChemBioChem. 2004 5 1508-1516. 

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