[3] Protein kinase phosphorylation site sequences and consensus specificity motifs: Tabulations

Pearson, Richard B.; Kemp, Bruce E.

doi:10.1016/0076-6879(91)00127-i

Cited by 1,007 publications

(541 citation statements)

References 129 publications

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“…The consensus sequences for substrate recognition are similar to both PKC and CaMKII. Although there are some exceptions, PKC phosphorylates the motif RXXS/TXR whereas CaMKII prefers RXXS/T (Pearson & Kemp, 1991). Moreover, we found similarities between the inhibition of CaMKII activity by transphosphorylation of PKC and by basal autophosphorylation of CaMKII.…”

Section: Discussionsupporting

confidence: 54%

Protein kinase C‐α attenuates cholinergically stimulated gastric acid secretion of rabbit parietal cells

Fährmann

Kaufhold

Pfeiffer³

et al. 2003

British J Pharmacology

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1 The phorbolester 12-O-tetradecanoyl phorbol-13-acetate (TPA), an activator of protein kinase C (PKC), inhibits cholinergic stimulation of gastric acid secretion. We observed that this effect strongly correlated with the inhibition of Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) activity in rabbit parietal cells. 2 The aim of this study was to specify the function of PKC-a in cholinergically stimulated H + secretion. PKC-a represents the only calcium-dependent PKC isoenzyme that has been detected in rabbit parietal cells. 3 Go¨6976, an inhibitor of calcium-dependent PKC, concentration-dependently antagonized the inhibitory effect of TPA, and, therefore, revealed the action of PKC-a on carbachol-induced acid secretion in rabbit parietal cells. 4 TPA exerted no additive inhibition of carbachol-stimulated acid secretion if acid secretion was partially inhibited by the potent CaMKII inhibitor 1-[N,O-bis(5-isoquinolinsulfonyl)-N-methyl-L-tyrosyl]-4-phenyl-piperazine (KN-62). 5 Since both kinase modulators, TPA and KN-62, affected no divergent signal transduction pathways in the parietal cell, an in vitro model has been used to study if PKC directly targets CaMKII. CaMKII purified from parietal cell-containing gastric mucosa of pig, was transphosphorylated by purified cPKC containing PKC-a up to 1.8 mol P i per mol CaMKII in vitro. The autonomy site of CaMKII was not transphosphorylated by PKC. 6 The phosphotransferase activity of the purified CaMKII was in vitro inhibited after transphosphorylation by PKC if calmodulin was absent during transphosphorylation. Attenuation of CaMKII activity by PKC showed strong similarity to the downregulation of CaMKII by basal autophosphorylation. 7 Our results suggest that PKC-a and CaMKII are closely functionally linked in a cholinergically induced signalling pathway in rabbit parietal cells. We assume that in cholinergically stimulated parietal cells PKC-a transinhibits CaMKII activity, resulting in an attenuation of acid secretion.

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Section: Discussionsupporting

confidence: 54%

Protein kinase C‐α attenuates cholinergically stimulated gastric acid secretion of rabbit parietal cells

Fährmann

Kaufhold

Pfeiffer³

et al. 2003

British J Pharmacology

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“…However, given the consensus sequences recognized by both PKA and PKC are structurally related (Pearson and Kemp, 1991), the possibility remained that the reactivity observed with the PKA substrate antibody resulted from cross-recognition of another phosphorylated serine residue. To address this, a polyclonal antibody was raised against a synthetic CD44 cytoplasmic domain peptide containing a phosphorylated serine at position 316 ( Figure 2a; see Materials and methods).…”

Section: Resultsmentioning

confidence: 99%

Directional sensing of a phorbol ester gradient requires CD44 and is regulated by CD44 phosphorylation

2006

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Cancer progression is associated with enhanced directional cell migration, both of the tumour cells invading into the stroma and stromal cells infiltrating the tumour site. In cell-based assays to study directional cell migration, phorbol esters are frequently used as a chemotactic agent. However, the molecular mechanism by which these activators of protein kinase C (PKC) result in the establishment of a polarized migratory phenotype is not known. Here we show that CD44 expression is essential for chemotaxis towards a phorbol ester gradient. In an investigation of CD44 phosphorylation kinetics in resting and stimulated cells, Ser316 was identified as a novel site of phosphorylation following activation of PKC. PKC does not phosphorylate Ser316 directly, but rather mediates the activation of downstream Ser316 kinase(s). In transfection studies, a phosphorylation-deficient Ser316 mutant was shown to act in a dominant-negative fashion to impair chemotaxis mediated by endogenous CD44 in response to a phorbol ester gradient. Importantly, this mutation had no effect on random cell motility or the ability of cells to migrate directionally towards a cocktail of chemoattractants. These studies demonstrate that CD44 functions to provide directional cues to migrating cells without affecting the motility apparatus.

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“…Two threonine residues are present in T51 at positions 471 and 484, but neither is present within obvious protein kinase consensus sequences. Peptide T52 contains two serine residues (Ser-490 and -491) that exist within a sequence characteristic of substrates of casein kinase II (Pearson & Kemp, 1991). One or both of these sites could be phosphorylated.…”

Section: Discussionmentioning

confidence: 99%

“…However, we believe it more likely that they are minor phosphorylated forms of 84R which, as in the case of 156R, migrate slightly slower than the unphosphorylated or underphosphorylated species. Several sites exist within the amino-terminal 79 residues of 496R that could serve as substrates for casein kinase II or members of the p34 ca~2 or MAP (mitogenactivated protein) kinase families (Pearson & Kemp, 1991). An additional 30K species was also observed, and because it was recognized by serum against protein IX and possibly 58-N1, it probably represents the 168R protein predicted by Lewis & Anderson (1987), Further studies involving both peptide mapping and analysis of mRNA will be required to confirm this possibility,…”

Section: Discussionmentioning

confidence: 99%

Characterization of the 55K adenovirus type 5 E1B product and related proteins

Takayesu

Teodoro

Whalen

et al. 1994

Journal of General Virology

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In addition to major proteins of 19K and 55K (176 and 496 residues, 176R and 496R, respectively), early region 1B (E1B) of human adenovirus type 5 (Ad5) is predicted to encode at least three other polypeptides of 156R, 93R and 84R that share 79 amino-terminal residues with 496R. We have used a series of specific antipeptide sera to identify and partially characterize these proteins. 84R was produced in large amounts, 156R somewhat less, and 93R at very low levels. Synthesis of 176R, 496R, as well as the E2A 72K DNA-binding protein commenced shortly after that of E1A proteins in Ad5-infected KB cells. Production of 156R, 93R and 84R began somewhat later, but prior to the synthesis of the late structural protein IX and hexon. 156R, which is composed of the 79 amino-terminal and 77 carboxy-terminal amino acids of 496R, migrated on SDS-PAGE as two species which appeared to differ by their degree of phosphorylation. 156R and 496R yielded identical tryptic phosphopeptides that contained both phosphoserine and phosphothreonine, and one of these was immunoprecipitated by a serum specific for the carboxy terminus. These results suggested that Ser-490 and/or Ser-491 as well as Thr-495 are major sites of phosphorylation in these proteins.

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[3] Protein kinase phosphorylation site sequences and consensus specificity motifs: Tabulations

Cited by 1,007 publications

References 129 publications

Protein kinase C‐α attenuates cholinergically stimulated gastric acid secretion of rabbit parietal cells

Protein kinase C‐α attenuates cholinergically stimulated gastric acid secretion of rabbit parietal cells

Directional sensing of a phorbol ester gradient requires CD44 and is regulated by CD44 phosphorylation

Characterization of the 55K adenovirus type 5 E1B product and related proteins

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