Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The existence of Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C), the effect of gastrin on phospholipid metabolism and guanylate cyclase activity were investigated to elucidate the cellular mechanism of action of gastrin on the corporal mucosa of the canine stomach. Protein kinase activity was determined by measuring the incorporation of [32P] into calf thymus H1-histone from [32P]-ATP. One unit of protein kinase was defined as the amount of enzyme which incorporated 1 pmol of phosphate from ATP into H1-histone. Protein kinase C was found in 100,000xg supernatant of homogenate fractionated by a DEAE-cellulose column chromatography. Characteristics of further purified protein kinase C, such as dependency on divalent cations and phospholipids, were in agreement with those of previously reported protein kinase C in other tissues. Furthermore, the gastric corporal mucosa was found to contain protein kinase C in large quantities. The specific activity of protein kinase C was 26,000 units/mg protein. The phospholipid metabolism was evaluated by the incorporation of [14C]-glycerol-3-phosphate and the change of the radioactivity of [32P] in individual phospholipids. Each phospholipid was extracted from the gastric corporal mucosa and isolated by thin layer chromatography. Guanylate cyclase activity was determined by measuring the cGMP produced, using radioimmunoassay. Gastrin significantly increased the incorporation of [14C]-glycerol-3-phosphate into phosphatidylethanolamine in the presence of acetylcholine (Ach). Ach increased the uptake of the tracer into phosphatidylinositol significantly, and the increase was enhanced by the simultaneous addition of gastrin. In the experiments with [32P]-labeled phospholipids, gastrin increased the incorporation of [32P] into phosphatidylethanolamine significantly. The significant increase of the radioactivity in phosphatidylinositol by Ach failed to be enhanced by gastrin, but that of phosphatidylethanolamine by Ach was enhanced by gastrin. No stimulation of guanylate cyclase activity by gastrin was detected in the dispersed gastric corporal mucosal cells. These results indicate that gastric corporal mucosa was one of the most abundant tissues in which protein kinase C was contained, when compared with various mammalian tissues previously reported by Minakuchi, Nishizuka, et al. Nishizuka et al, recently proposed the novel hypothesis that phosphatidylinositol turnover activated by cAMP-independent agonists will be essentially required to activate protein kinase C. Our results suggest that gastrin can provoke phospholipids turnover including phosphatidylinositol turnover in gastric corporal mucosa. Therefore, our data indicate the possibility that the protein kinase C system plays an important role in the cellular mechanism of action of gastrin on gastric corporal mucosa.
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PMID:[The cellular mechanism of action of gastrin on the corporal mucosa of the canine stomach. (2) Ca2+-activated, phospholipid-dependent protein kinase and phospholipid turnover--possible mediator of gastrin action]. 613 23

Protein kinase D2 (PKD2) belongs to the PKD family of serine/threonine kinases that is activated by phorbol esters and G protein-coupled receptors (GPCRs). Its C-terminal regulatory domain comprises two cysteine-rich domains (C1a/C1b) followed by a pleckstrin homology (PH) domain. Here, we examined the role of the regulatory domain in PKD2 phorbol ester binding, catalytic activity, and subcellular localization: The PH domain is a negative regulator of kinase activity. C1a/C1b, in particular C1b, is required for phorbol ester binding and gastrin-stimulated PKD2 activation, but it has no inhibitory effect on the catalytic activity. Gastrin triggers nuclear accumulation of PKD2 in living AGS-B cancer cells. C1a/C1b, not the PH domain, plays a complex role in the regulation of nucleocytoplasmic shuttling: We identified a nuclear localization sequence in the linker region between C1a and C1b and a nuclear export signal in the C1a domain. In conclusion, our results define the critical components of the PKD2 regulatory domain controlling phorbol ester binding, catalytic activity, and nucleocytoplasmic shuttling and reveal marked differences to the regulatory properties of this domain in PKD1. These findings could explain functional differences between PKD isoforms and point to a functional role of PKD2 in the nucleus upon activation by GPCRs.
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PMID:Role of the regulatory domain of protein kinase D2 in phorbol ester binding, catalytic activity, and nucleocytoplasmic shuttling. 1597