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Gene Review

PIK3C2A  -  phosphatidylinositol-4-phosphate 3-kinase,...

Homo sapiens

Synonyms: CPK, PI3-K-C2(ALPHA), PI3-K-C2A, PI3K-C2-alpha, PI3K-C2alpha, ...
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Disease relevance of PIK3C2A

  • Finally, intravenous wortmannin infusion induced sustained hypotension in rats, with inhibition of PI3K-C2alpha activity, GTP-loading of Rho and MYPT1 phosphorylation in the artery [1].
  • CPK values in Parkinson's disease [2].
  • Serial CPK determinations for evaluation of size and development of acute myocardial infarction [3].
  • We conclude 1) new Q waves on ECG underestimate the incidence of myocardial damage after coronary artery surgery; 2) MB-CPK alone overestimates the incidence of infarction; and 3) a combination of the three techniques is the best means for detecting myocardial damage after coronary artery bypass graft surgery [4].
  • Other selected variables--sex, CPK ratio and history of smoking, diabetes and hypertension--appear to be less clearly associated with ventricular arrhythmia [5].

Psychiatry related information on PIK3C2A

  • The relationship between wrist-monitored motor activity and serum CPK activity in psychiatric in-patients [6].
  • Physical stress will raise CPK, but the role of psychological stress has been unclear [7].
  • Thus certain clinical and laboratory features such as anterior site of infarction, higher serum level of CPK and CPK-MB and severe alterations of left ventricular kinesis proved to be useful in identifying a subset of patients most likely to have LVT who may benefit from early anticoagulant therapy [8].
  • In all patients there were elevated CPK levels, histological evidence of an acute myopathy, heavy alcohol intake prior to the development of symptoms, and improvement in hospital with the cessation of alcohol consumption [9].
  • Furthermore, subjects with AMS on day 1 at BC were characterized by a greater decrease in the resting pain threshold and greater increase in resting LH, CPK and myoglobin compared with subjects without AMS (p < 0.05) [10].

High impact information on PIK3C2A

  • Further, we show that endogenous PI3K-C2alpha is localized in coated pits and that exogenous expression affects clathrin-mediated endocytosis and sorting in the trans-Golgi network [11].
  • Increased serum creatine kinase (CPK) activity has been reported to be present during acute exacerbations of psychosis in the majority of patients with the major "functional" psychoses [12].
  • High mean serum CPK activity may be an indication of an increase in permeability of the muscle cell membrane, which in turn may be due to some defect in the neurotrophic regulation of muscle physiology or an independent expression of muscle abnormalities [12].
  • The mean serum CPK level was also correlated with the terminal innervation ratio, an indication of alpha motor neuron dysfunction [12].
  • The heart temperature was kept at 10 degrees to 15 degrees C. Patients were evaluated intraoperatively and postoperatively for (1) supraventricular tachycardia, (2) ECG changes, (3) lactate dehydrogenase and total CPK and isoenzyme (MB) studies, and (4) hemodynamic studies in the intensive care unit [13].

Chemical compound and disease context of PIK3C2A


Biological context of PIK3C2A

  • Further, a specific binding site was identified for clathrin on the N terminus of PI3K-C2alpha, whose occupancy resulted in lipid kinase activation [19].
  • Biochemical analysis of recombinant PI3-K-C2 alpha demonstrates a restricted lipid substrate specificity [20].
  • Left ventricular ejection fraction (EF) and percent akinesis (%A) were calculated from gated cardiac blood pool scans; myocardial infarct size was estimated from peak CPK values; and VPCs were detected by 24 hour ambulatory ECGs 2-4 weeks following hospitalization for acute MI [21].
  • CP/CPK or aspirin alone reduced fibrinogen binding to 20% to 30%; however, this binding was sufficient to support full platelet aggregation [22].
  • Here, we have identified a role for phosphatidylinositol 3-kinase C2alpha (PI3K-C2alpha) and its main catalytic product, PtdIns3P, in regulated exocytosis [23].

Anatomical context of PIK3C2A


Associations of PIK3C2A with chemical compounds

  • Neither the phospholipid association nor the subcellular localization of PI3K-C2alpha was dependent upon either its COOH-terminal PX or C2 domains [24].
  • Phosphoinositide 3-kinase C2alpha (PI3K-C2alpha) belongs to the class II phosphatidylinositol 3-kinases, which are defined by their in vitro usage of phosphatidylinositol and phosphatidylinositol 4-phosphate as substrates [26].
  • Treatment of cells with brefeldin A disrupted the perinuclear staining pattern of both PI3K-C2alpha and the AP-1 complex demonstrating that the localization of both molecules at the TGN is dependent upon ADP-ribosylation factor GTPase activity [24].
  • The catalytic activity of PI3-K-C2 alpha is refractory to concentrations of wortmannin and LY294002 which inhibit the PI3-K activity of other family members [20].
  • These observations indicate that cAMP inhibits Ca(2+)-mediated activation of the MLCP-regulating signaling pathway comprising PI3K-C2alpha, Rho, and Rho kinase in a manner independent of Ca(2+) and point to the novel mechanism of the cAMP actions in the regulation of vascular smooth muscle contraction [27].

Regulatory relationships of PIK3C2A


Other interactions of PIK3C2A


Analytical, diagnostic and therapeutic context of PIK3C2A

  • Finally, immunoprecipitation experiments reveal an interaction between endogenous PI3K-C2alpha and dynactin subunits [25].
  • In this report, we present evidence for an association between the presence of a transient elevation of serum CPK activity beyond the upper limit of normal during psychotic episodes and relatively high mean serum CPK levels during the rest of hospitalization [12].
  • Physician decision was based upon history and once-daily ECG and total enzymes (CPK, SGOT, LDH) [31].
  • LDH, CPK isoenzymes, and myocardial scintigraphy did not reveal myocardial damage [32].
  • The diagnostic accuracy of creatine kinase (CPK), erythrocyte sedimentation rate, antinuclear antibody, and electromyography (EMG) were compared with the gold standard muscle biopsy [33].


  1. Class II phosphoinositide 3-kinase alpha-isoform regulates Rho, myosin phosphatase and contraction in vascular smooth muscle. Wang, Y., Yoshioka, K., Azam, M.A., Takuwa, N., Sakurada, S., Kayaba, Y., Sugimoto, N., Inoki, I., Kimura, T., Kuwaki, T., Takuwa, Y. Biochem. J. (2006) [Pubmed]
  2. CPK values in Parkinson's disease. Tanner, C.M., Goetz, C.G. N. Engl. J. Med. (1981) [Pubmed]
  3. Serial CPK determinations for evaluation of size and development of acute myocardial infarction. Bleifeld, W.H., Hanrath, P., Mathey, D. Circulation (1976) [Pubmed]
  4. Detection of perioperative myocardial damage after coronary artery bypass graft surgery. Righetti, A., Crawford, M.H., O'Rourke, R.A., Hardarson, T., Schelbert, H., Daily, P.O., DeLuca, M., Ashburn, W., Ross, J. Circulation (1977) [Pubmed]
  5. Effect of propranolol on ventricular arrhythmia. The beta-blocker heart attack trial experience. Lichstein, E., Morganroth, J., Harrist, R., Hubble, E. Circulation (1983) [Pubmed]
  6. The relationship between wrist-monitored motor activity and serum CPK activity in psychiatric in-patients. Goode, D.J., Meltzer, H.Y., Moretti, R., Kupfer, D.J., McPartland, R.J. The British journal of psychiatry : the journal of mental science. (1979) [Pubmed]
  7. CPK: relationship of psychological and physical stress. Rich, C.L., Woodrow, K.M., Gillin, J.C. Diseases of the nervous system. (1977) [Pubmed]
  8. Left ventricular thrombus and myocardial infarction. Gianrossi, R., Marruzzo, M., Torrielli, A., Azzolini, A., Nizzo, M.C., Montemanni, M., Mottola, G. Acta cardiologica. (1985) [Pubmed]
  9. The effect of ethyl alcohol on striated muscle: some clinical and pathological observations. Walsh, J.C., Conomy, A.B. Australian and New Zealand journal of medicine. (1977) [Pubmed]
  10. A potential role for free radical-mediated skeletal muscle soreness in the pathophysiology of acute mountain sickness. Bailey, D.M., Davies, B., Young, I.S., Hullin, D.A., Seddon, P.S. Aviation, space, and environmental medicine. (2001) [Pubmed]
  11. The class II phosphoinositide 3-kinase C2alpha is activated by clathrin and regulates clathrin-mediated membrane trafficking. Gaidarov, I., Smith, M.E., Domin, J., Keen, J.H. Mol. Cell (2001) [Pubmed]
  12. Mean serum creatine kinase activity in patients with functional psychoses. Meltzer, H.Y., Ross-Stanton, J., Schlessinger, S. Arch. Gen. Psychiatry (1980) [Pubmed]
  13. Comparison of cold versus warm cardioplegia. Crystalloid antegrade or retrograde blood? Lajos, T.Z., Espersen, C.C., Lajos, P.S., Fiedler, R.C., Bergsland, J., Joyce, L.T. Circulation (1993) [Pubmed]
  14. Radioimmunoassay of creatine kinase-B isoenzyme in human sera: results in patients with acute myocardial infarction. Willerson, J.T., Stone, M.J., Ting, R., Mukherjee, A., Gomez-Sanchez, C.E., Lewis, P., Hersh, L.B. Proc. Natl. Acad. Sci. U.S.A. (1977) [Pubmed]
  15. Scintigraphic, electrocardiographic, and enzymatic diagnosis of perioperative myocardial infarction in patients undergoing myocardial revascularization. Burdine, J.A., DePuey, E.G., Orzan, F., Mathur, V.S., Hall, R.J. J. Nucl. Med. (1979) [Pubmed]
  16. DeltaPKC-mediated activation of epsilonPKC in ethanol-induced cardiac protection from ischemia. Inagaki, K., Mochly-Rosen, D. J. Mol. Cell. Cardiol. (2005) [Pubmed]
  17. Acute phencyclidine intoxication: incidence of clinical findings in 1,000 cases. McCarron, M.M., Schulze, B.W., Thompson, G.A., Conder, M.C., Goetz, W.A. Annals of emergency medicine. (1981) [Pubmed]
  18. Neutrophil tolerance to oxidative stress induced by hypoxia/reoxygenation. Sureda, A., Batle, J.M., Tauler, P., Cases, N., Aguiló, A., Tur, J.A., Pons, A. Free Radic. Res. (2004) [Pubmed]
  19. Individual phosphoinositide 3-kinase C2alpha domain activities independently regulate clathrin function. Gaidarov, I., Zhao, Y., Keen, J.H. J. Biol. Chem. (2005) [Pubmed]
  20. Cloning of a human phosphoinositide 3-kinase with a C2 domain that displays reduced sensitivity to the inhibitor wortmannin. Domin, J., Pages, F., Volinia, S., Rittenhouse, S.E., Zvelebil, M.J., Stein, R.C., Waterfield, M.D. Biochem. J. (1997) [Pubmed]
  21. Ventricular arrhythmias in the late hospital phase of acute myocardial infarction. Relation to left ventricular function detected by gated cardiac blood pool scanning. Schulze, R.A., Rouleau, J., Rigo, P., Bowers, S., Strauss, H.W., Pitt, B. Circulation (1975) [Pubmed]
  22. Exposure of platelet fibrinogen receptors by a monoclonal antibody to CD9 antigen. Hato, T., Ikeda, K., Yasukawa, M., Watanabe, A., Kobayashi, Y. Blood (1988) [Pubmed]
  23. Phosphatidylinositol 3-kinase C2alpha is essential for ATP-dependent priming of neurosecretory granule exocytosis. Meunier, F.A., Osborne, S.L., Hammond, G.R., Cooke, F.T., Parker, P.J., Domin, J., Schiavo, G. Mol. Biol. Cell (2005) [Pubmed]
  24. The class II phosphoinositide 3-kinase PI3K-C2alpha is concentrated in the trans-Golgi network and present in clathrin-coated vesicles. Domin, J., Gaidarov, I., Smith, M.E., Keen, J.H., Waterfield, M.D. J. Biol. Chem. (2000) [Pubmed]
  25. Phosphoinositide 3-Kinase C2{alpha} Links Clathrin to Microtubule-dependent Movement. Zhao, Y., Gaidarov, I., Keen, J.H. J. Biol. Chem. (2007) [Pubmed]
  26. Phosphatidylinositol 3-kinase c2alpha contains a nuclear localization sequence and associates with nuclear speckles. Didichenko, S.A., Thelen, M. J. Biol. Chem. (2001) [Pubmed]
  27. Ca2+-Independent, Inhibitory Effects of Cyclic Adenosine 5'-Monophosphate on Ca2+ Regulation of Phosphoinositide 3-Kinase C2{alpha}, Rho, and Myosin Phosphatase in Vascular Smooth Muscle. Azam, M.A., Yoshioka, K., Ohkura, S., Takuwa, N., Sugimoto, N., Sato, K., Takuwa, Y. J. Pharmacol. Exp. Ther. (2007) [Pubmed]
  28. The CC chemokine monocyte chemotactic peptide-1 activates both the class I p85/p110 phosphatidylinositol 3-kinase and the class II PI3K-C2alpha. Turner, S.J., Domin, J., Waterfield, M.D., Ward, S.G., Westwick, J. J. Biol. Chem. (1998) [Pubmed]
  29. Class II phosphoinositide 3-kinases are downstream targets of activated polypeptide growth factor receptors. Arcaro, A., Zvelebil, M.J., Wallasch, C., Ullrich, A., Waterfield, M.D., Domin, J. Mol. Cell. Biol. (2000) [Pubmed]
  30. Recruitment of the class II phosphoinositide 3-kinase C2beta to the epidermal growth factor receptor: role of Grb2. Wheeler, M., Domin, J. Mol. Cell. Biol. (2001) [Pubmed]
  31. Diagnosis of acute myocardial infarction in a community hospital: significance of CPK-MB determination. Roark, S.F., Wagner, G.S., Izlar, H.L., Roe, C.R. Circulation (1976) [Pubmed]
  32. ST-segment elevation with elective DC cardioversion. Chun, P.K., Davia, J.E., Donohue, D.J. Circulation (1981) [Pubmed]
  33. Biomechanics, diagnosis, and treatment outcome in inflammatory myopathy presenting as oropharyngeal dysphagia. Williams, R.B., Grehan, M.J., Hersch, M., Andre, J., Cook, I.J. Gut (2003) [Pubmed]
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