Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. In isolated rat adipocytes, acetyl-CoA carboxylase is inactivated by treatment of the cells with adrenaline or the beta-agonist isoproterenol, but not by the alpha-agonist phenylephrine. The inactivation is stable during purification in the presence of protein phosphatase inhibitors, and is associated with a 30-40% increase in the labelling of enzyme isolated from 32P-labelled cells. 2. Increased phosphorylation occurs within peptide T1, which was identified by sequencing to be the peptide Ser-Ser77-Met-Ser79-Gly-Leu-His-Leu-Val-Lys, containing Ser-77 (phosphorylated by cyclic-AMP-dependent protein kinase) and Ser-79 (phosphorylated by the AMP-activated protein kinase). Analysis of the release of radioactivity as free phosphate during Edman degradation of peptide T1 revealed that all of the phosphate was in Ser-79 in both basal and hormone- or agonist-stimulated cells. Treatment of adipocytes with various agents which activate cyclic-AMP-dependent protein kinase by receptor-independent mechanisms (forskolin, cyclic AMP analogues, isobutylmethylxanthine) also produced inactivation of acetyl-CoA carboxylase and increased phosphorylation at Ser-79. 3. The (Rp)-[thio]phosphate analogue of cyclic AMP, which is an antagonist of binding of cyclic AMP to the regulatory subunit of cyclic-AMP-dependent protein kinase, opposes the effect of adrenaline on phosphorylation and inactivation of acetyl-CoA carboxylase. Together with the effects of isobutylmethylxanthine and the stimulatory cyclic AMP analogues, this strongly indicates that cyclic-AMP-dependent protein kinase is an essential component of the signal transduction pathway, although clearly it does not directly phosphorylate acetyl-CoA carboxylase. 4. As shown by okadaic acid inhibition, greater than 95% of the acetyl-CoA carboxylase phosphatase activity in extracts of rat adipocytes or liver is accounted for by protein phosphatase-2A, with less than 5% attributable to protein phosphatase-1. Inhibition of protein phosphatase-1 via phosphorylation of inhibitor-1 is therefore unlikely to be the mechanism by which cyclic-AMP-dependent protein kinase indirectly increases phosphorylation of acetyl-CoA carboxylase. Various other potential mechanisms are discussed.
...
PMID:Roles of the AMP-activated and cyclic-AMP-dependent protein kinases in the adrenaline-induced inactivation of acetyl-CoA carboxylase in rat adipocytes. 168 96

Among various phosphate acceptor proteins and peptides so far tested, a synthetic peptide having the sequence surrounding Ser(8) of myelin basic protein, Gln-Lys-Arg-Pro-Ser(8)-Gln-Arg-Ser-Lys-Tyr-Leu, (MBP4-14), is the most specific and convenient substrate which can be used for selective assay of protein kinase C. This peptide is not phosphorylated by cyclic AMP-dependent protein kinase, casein kinases I and II, Ca2+/calmodulin-dependent protein kinase II, or phosphorylase kinase, and can be routinely used for the assay of protein kinase C with low background in the crude tissue extracts. The Km value is considerably low (7 microM) with a Vmax value of twice as much as that for H1 histone.
...
PMID:A synthetic peptide substrate for selective assay of protein kinase C. 168 74

The synthetic phosphotyrosyl tridecapeptide H-Arg-Leu-Ile-Glu-Asp-Asn-Glu-Tyr(P)-Thr-Ala-Arg-Gln-Gly-OH, reproducing a major phosphoacceptor site of protein tyrosine kinases of the src-family, can be phosphorylated at Thr-9 by both casein kinases -1 and -2. Its shorter derivative H-Asn-Glu-Tyr(P)-Thr-Ala-OH is not affected by casein kinase-1 while representing a substrate as good as the tridecapeptide for casein kinase-2. The unphosphorylated analogue H-Asn-Glu-Tyr-Thr-Ala-OH, however, is a much poorer substrate, and no significant phosphorylation could be observed of its O-methyl ether derivative H-Asn-Glu-Tyr(Me)-Thr-Ala-OMe. These data on one side corroborate the concept that casein kinase-1 recognizes residues located on the C-terminal edge of acidic stretches, providing, on the other, the evidence that phosphotyrosyl side chains can act as specificity determinants for casein kinase-2.
...
PMID:Phosphorylation of src-phosphopeptides by casein kinases-1 and -2: favourable effect of phosphotyrosine. 169 74

Protein kinase C is a family of multifunctional protein serine/threonine kinase and generally accepted to be involved in a wide variety of cellular signal transduction. Biochemical and immunochemical studies as well as sequence analysis of its cDNA clones have revealed the existence of multiple subspecies of this enzyme with obvious tissue-specific expression. Enzymatic properties of type I, II, and III protein kinase C subspecies, which are encoded by gamma-, beta I- and beta II, and alpha-cDNA, respectively, are well characterized. Many proteins and peptides are reported as phosphate acceptors of these protein kinase C subspecies. In this study, it is shown that a synthetic peptide, Gln-Lys-Arg-Pro-Ser-Gln-Arg-Ser-Lys-Tyr-Leu, which corresponds to amino acid residues 4-14 of bovine myelin basic protein, is the most specific and convenient substrate for selective assay of protein kinase C among various phosphate acceptor proteins and peptides. This peptide is phosphorylated at Ser-8, but not Ser-11 by protein kinase C subspecies in a manner dependent on Ca2+, phosphatidylserine, and diacylglycerol. This peptide is not phosphorylated by other protein serine/threonine kinases such as cyclic AMP-dependent protein kinase. Thus, it is possible to assay protein kinase C activity in the crude tissue extracts selectively using this peptide as a phosphate acceptor.
...
PMID:Selective assay of protein kinase C with a specific peptide substrate. 172 Aug 27

The primary structure of bovine rhodopsin kinase (RK), which phosphorylates light-activated rhodopsin (Rho*), terminates with the amino acid sequence Cys558-Val-Leu-Ser561, a motif that has been shown to direct the isoprenylation and alpha-carboxyl methylation of many proteins (e.g. p21Ha-ras). Transient expression of RK in COS-7 cells revealed the presence of two immunoreactive protein species. Consistent with RK being modified by isoprenylation, interconversion of these two species was dependent upon isoprenoid biosynthesis in the cells. Moreover, a serine substitution for Cys558 resulted in a single RK species whose migration on sodium dodecyl sulfate-polyacrylamide gels was identical to that of RK from cells treated with mevinolin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and, thus, of isoprenoid biosynthesis. This finding indicates that isoprenylation of RK requires Cys558. The electrophoretic mobility of isoprenylated RK synthesized in COS-7 cells was identical to that of RK from bovine rod outer segments, suggesting that RK is isoprenylated in vivo. RK was determined to be modified by a farnesyl moiety and alpha-carboxyl-methylated. A time course of Rho* phosphorylation revealed that non-processed RK is approximately 4-fold less active than wild-type RK. This is the first demonstration of isoprenylation/alpha-carboxyl methylation of a protein kinase, and suggests that these modifications markedly influence enzymatic activity in vivo.
...
PMID:Isoprenylation of a protein kinase. Requirement of farnesylation/alpha-carboxyl methylation for full enzymatic activity of rhodopsin kinase. 173 Jun 92

p19 is a highly conserved 19-kDa cytosolic protein that undergoes phosphorylation in mammalian cells upon activation of several distinct signal transduction pathways. Its expression is widespread but developmentally regulated. To determine the in vivo phosphorylation site(s) of p19, the protein was purified from bovine brain and resolved into the unphosphorylated form (p19) and a mixture of the two predominant phospho-forms (pp19). Proteolytic fragments of p19 and pp19 were examined by liquid chromatography/mass spectrometry (LC/MS). We detected ion masses corresponding to fragments spanning the entire amino acid sequence as deduced from the cDNA except for those predicted to contain an unmodified amino terminus. Instead, the digests revealed ions corresponding to peptides lacking the initiator methionine and containing an N-acetylated alanine at the amino terminus. The analysis of pp19, but not that of p19, revealed two sets of ions representing peptides whose m/z values differed by 80 atomic mass units, the incremental mass of a phosphate residue. These putative phosphate-bearing peptides were sensitive to alkaline phosphatase treatment. Using combined trypsin and V8 protease digestions, the phosphorylation sites were mapped to Ser-25 and Ser-38, in the peptides Leu-Ile-Leu-Ser*-Pro-Arg and Phe-Pro-Leu-Ser*-Pro-Pro-Lys, respectively. Interestingly, both phosphoserines are in a very similar sequence context, suggesting that a single proline-directed serine protein kinase, possibly p34cdc2, is responsible for phosphorylation of both sites in vivo.
...
PMID:Analysis of phosphoprotein p19 by liquid chromatography/mass spectrometry. Identification of two proline-directed serine phosphorylation sites and a blocked amino terminus. 173 1

The substrate specificity determinants of a protease-activated protein kinase from rat liver, termined PAK-1, have been investigated using peptide analogues of the ribosomal protein S6 sequence: Ala229-Lys-Arg-Arg-Arg-Leu-Ser-Ser-Leu-Arg-Ala-Ser-Thr-Ser-Lys- Ser244. Low peptide substrate Km's and a preference for Ser236 were attributed to a combination of sequence determinants located in the vicinity of this site. Thus, Km's are increased appreciably with analogues in which the N-terminal cluster of basic residues is reduced or where alanine is substituted for Arg238. Even more dramatic effects are elicited by alanine substitution of one of the adjacent serine residues, resulting in 20-fold to 800-fold increases in the Km's for the [Ala235] and [Ala236] S6(229-239) variants, respectively. Arg238 is the major specificity determinant of the Ser236 site, with little detectable phosphorylation of Ser236 occurring in the [Ala238] S6(229-239) substrate. Ser235 phosphorylation is also selectively enhanced by the addition of N-terminal basic residues to the Arg-Arg-Leu-Ser-Ser-Leu-Arg-Ala analogue. Finally, multiple phosphorylation events are influenced by negative cooperativity between the Ser235 and Ser236 sites and positive cooperativity between the Ser236 and Ser240 sites. The general S6 peptide substrate determinants for liver PAK-1 resembled those for brain protein kinase C and another major liver PAK, termed PAK-2. However, subtle differences observed between the kinetic properties with individual S6 peptide substrates distinguished PAK-1 from the other enzymes. More striking differences were observed between the liver PAKs and cyclic AMP-dependent protein kinase (cAK), particularly with respect to the cAK's relatively poor S6 peptide substrate kinetics, its preference for Ser235 and its ability to more extensively phosphorylate multiple sites in the S6 peptides.
...
PMID:Determinants of multi-site phosphorylation of peptide analogues of ribosomal protein S6 by novel protease-activated protein kinases. 182 86

The plant hormone ethylene mediates a number of developmental processes and responses to environmental stress in higher plants. Our research efforts over the last three years have been focused on developing an understanding of the molecular basis of ethylene action in plants. To this end, we have isolated mutants in Arabidopsis thaliana with altered responses to ethylene. One such mutant, designated etr, shows no measurable responses to ethylene and has reduced ethylene binding in leaf tissue indicating that the mutation may directly affect the ethylene receptor. We have genetically mapped the etr mutation and by chromosome walking have isolated an 18 kb fragment of genomic DNA that contains the mutant gene. Sequence analysis of cDNAs which map to the 18 kb fragment has produced a candidate for the ETR gene which codes for a putative transmembrane protein kinase. Sequence analysis indicates a domain composed of 9 copies of a 23 amino acid leucine-rich repeat unit and a domain containing a serine/threonine type protein kinase. These two domains are separated by a single 24 amino acid hydrophobic domain. A model is presented that describes the possible mechanism of action of the protein kinase with respect to ethylene-mediated responses in plants.
...
PMID:Genetic analysis of ethylene responses in Arabidopsis thaliana. 184 6

We identified the sites on vimentin that are phosphorylated by Ca2(+)-calmodulin-dependent protein kinase II (CaM-kinase II). Sequential analysis of the purified phosphopeptides demonstrated that the sites are -Thr-Arg-Thr-Tyr-Ser(PO4)38-Leu-Gly-Ser-Ala- and -Val-Arg-Leu-Leu-Gln-Asp-Ser(PO4)82-Val-Asp-, which are located within the amino-terminal head domain of vimentin. For Ser-82 but not Ser-38, the proposed CaM-kinase II recognition amino acid sequence (Arg-X-X-Ser/Thr) was not found. Studies with a series of synthetic peptide analogs corresponding to Ser-82 and its surrounding amino acid sequence indicate that Asp-84 acts as an essential substrate specificity determinant for the Ser-82 phosphorylation by CaM-kinase II. The CaM-kinase II recognition site may be more extensive than heretofore determined.
...
PMID:Evidence that Ser-82 is a unique phosphorylation site on vimentin for Ca2(+)-calmodulin-dependent protein kinase II. 185 Sep 97

The type II cAMP-dependent protein kinase is localized to specific subcellular environments through the binding of the regulatory subunit (RII) dimer to RII-anchoring proteins. Computer-aided analysis of secondary structure, performed on four RII-anchoring protein sequences (the microtubule-associated protein 2, P150, and two thyroid proteins Ht 21 and Ht 31), has identified common regions of approximately 14 residues which display high probabilities of forming amphipathic helices. The potential amphipathic helix region of Ht 31 (Leu-Ile-Glu-Glu-Ala-Ala-Ser-Arg-Ile-Val-Asp-Ala-Val-Ile) lies between residues 494 and 507. A bacterially expressed 318-amino acid fragment, Ht 31 (418-736), containing the amphipathic helix region, was able to bind RII alpha. Site-directed mutagenesis designed to disrupt the secondary structure in the putative binding helix reduced binding dramatically. Specifically, substitution of proline for Ala-498 significantly diminished RII alpha binding, and similar mutation of Ile-502 or Ile-507 abolished interaction. Mutation of Ala-522 to proline, which is located outside the predicted amphipathic helix region, had no effect on RII alpha binding. These data suggest that anchoring proteins interact with RII alpha via an amphipathic helix binding motif.
...
PMID:Interaction of the regulatory subunit (RII) of cAMP-dependent protein kinase with RII-anchoring proteins occurs through an amphipathic helix binding motif. 186 Aug 36


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---