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Gene Review

Pik3c2a  -  phosphatidylinositol 3-kinase, C2 domain...

Mus musculus

Synonyms: Cpk, Cpk-m, PI3K-C2-alpha, PI3KC2, Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha, ...
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Disease relevance of Pik3c2a


High impact information on Pik3c2a

  • The amino acid sequence of peptides from p170 reveal its identity to early endosomal antigen (EEA) 1, an endosomal antigen with homology to several yeast proteins genetically implicated in membrane trafficking [2].
  • Immunofluorescence analysis of 3T3-L1 adipocytes with antisera against p170/EEA1 reveal a punctate peripheral pattern that becomes diffuse in response to wortmannin [2].
  • [Dev. Biol., 219, 250-258 (2000)] showed that reduced dosage of Pax2 caused increased apoptosis, and ameliorated cystogenesis in Cpk mutant mice with recessive PKD [3].
  • We found that p170 translation was dramatically reduced by mimosine due to its iron-chelating function [4].
  • The decreased expression of p170 by mimosine caused diminished de novo synthesis of tyrosinated alpha-tubulin and elevated translation of p27 before cell cycle arrest [4].

Biological context of Pik3c2a

  • The amino acid sequences of Cpk and Cpk-m are most similar to that of p110, a family of PtdIns 3-kinases that mediates the responses of cells to mitogenic stimuli [5].
  • Biochemical analysis of recombinant PI3-K-C2 alpha demonstrates a restricted lipid substrate specificity [6].
  • When quiescent cells were stimulated with serum, the p170 level began to increase at 12 h and reached a maximal level at 24-28 h, corresponding to the G2 phase [7].
  • These observations suggest that p170 is likely an early response gene to mimosine treatment and a mediator for mimosine effect on mRNA translation [4].
  • These observations, together with our previous findings, suggest that p170 may regulate the translation of a subset mRNAs and its elevated expression level may be important for cancer cell growth and for maintaining their malignant phenotype [1].

Anatomical context of Pik3c2a

  • We report here the cloning of a novel PI 3-kinase, p170, from cDNA of insulin-sensitive mouse 3T3-L1 adipocytes [8].
  • The fluctuations in the expression of two forms of DNA topoisomerase II, p170 and p180, were examined by immunoblotting during the transition of the growth state and the cell cycle in Swiss 3T3 cells [7].
  • Normal renal epithelial cells express p170 as a function of their secretory duties therefore this human tissue was used as a positive tissue control in our immunocytochemical study [9].

Associations of Pik3c2a with chemical compounds

  • Mouse p170 is a novel phosphatidylinositol 3-kinase containing a C2 domain [8].
  • Mouse p170 is also distinct from PtdIns 3-kinase or the p110 PI 3-kinases in exhibiting a 10-fold lower sensitivity to wortmannin [8].
  • 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 [6].
  • In spite of these functional similarities, 8-MOC, caffeine and 8-CC were unable to stimulate the formation of a cleavable complex by purified L1210 topoisomerase II (p170 form) when SV40 DNA and human c-myc DNA were used as substrate [10].
  • The stimulation by leptin was not accompanied by recruitment of any tyrosine phosphorylated proteins to PI3K-C2alpha and no shift in electrophoretic mobility was noted [11].

Analytical, diagnostic and therapeutic context of Pik3c2a

  • These statistically significant immunocytochemical results suggest a direct correlation between the quantitative presence of p170 glycoprotein in human OS cells and the efficacy of the employed chemotherapy [9].


  1. Role of eIF3 p170 in controlling synthesis of ribonucleotide reductase M2 and cell growth. Dong, Z., Liu, L.H., Han, B., Pincheira, R., Zhang, J.T. Oncogene (2004) [Pubmed]
  2. Identification of an early endosomal protein regulated by phosphatidylinositol 3-kinase. Patki, V., Virbasius, J., Lane, W.S., Toh, B.H., Shpetner, H.S., Corvera, S. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  3. Pax2 gene dosage influences cystogenesis in autosomal dominant polycystic kidney disease. Stayner, C., Iglesias, D.M., Goodyer, P.R., Ellis, L., Germino, G., Zhou, J., Eccles, M.R. Hum. Mol. Genet. (2006) [Pubmed]
  4. EIF3 p170, a mediator of mimosine effect on protein synthesis and cell cycle progression. Dong, Z., Zhang, J.T. Mol. Biol. Cell (2003) [Pubmed]
  5. Cpk is a novel class of Drosophila PtdIns 3-kinase containing a C2 domain. Molz, L., Chen, Y.W., Hirano, M., Williams, L.T. J. Biol. Chem. (1996) [Pubmed]
  6. 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]
  7. Growth state- and cell cycle-dependent fluctuation in the expression of two forms of DNA topoisomerase II and possible specific modification of the higher molecular weight form in the M phase. Kimura, K., Saijo, M., Ui, M., Enomoto, T. J. Biol. Chem. (1994) [Pubmed]
  8. Mouse p170 is a novel phosphatidylinositol 3-kinase containing a C2 domain. Virbasius, J.V., Guilherme, A., Czech, M.P. J. Biol. Chem. (1996) [Pubmed]
  9. Immunocytochemical observation of multidrug resistance (MDR) p170 glycoprotein expression in human osteosarcoma cells. The clinical significance of MDR protein overexpression. Bodey, B., Taylor, C.R., Siegel, S.E., Kaiser, H.E. Anticancer Res. (1995) [Pubmed]
  10. Production of protein-associated DNA breaks by 8-methoxycaffeine, caffeine and 8-chlorocaffeine in isolated nuclei from L1210 cells: comparison with those produced by topoisomerase II inhibitors. Russo, P., Poggi, L., Parodi, S., Pedrini, A.M., Kohn, K.W., Pommier, Y. Carcinogenesis (1991) [Pubmed]
  11. TNF-alpha and leptin activate the alpha-isoform of class II phosphoinositide 3-kinase. Ktori, C., Shepherd, P.R., O'Rourke, L. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
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