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Journal of Biochemistry Advance Access originally published online on October 30, 2008
Journal of Biochemistry 2009 145(1):87-94; doi:10.1093/jb/mvn142
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© The Authors 2008. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved

Negative Regulation of Class IA Phosphoinositide 3-kinase by Protein Kinase C{delta} Limits Fc{gamma} Receptor-Mediated Phagocytosis in Macrophages

Kaoru Hazeki*, Kazumi Inoue, Kiyomi Nigorikawa and Osamu Hazeki

Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima 734-8553, Japan

*To whom correspondence should be addressed. Tel: +81-82-257-5308, Fax: +81-82-257-5309, E-mail: khazeki{at}hiroshima-u.ac.jp

Received September 22, 2008; Accepted October 21, 2008


  Abstract

Stimulation of macrophages by various ligands results in the activation of both phosphoinositide 3-kinase (PI3K) and protein kinase C (PKC). Here, we showed that PKC{delta} selectively inhibits class IA PI3K. Prior exposure of macrophages to a PKC activator, phorbol 12-myristate 13-acetate (PMA) inhibited the PI3K activation induced by the Fc{gamma} receptor (Fc{gamma}R) ligation but not that induced by C5a. Prolonged PKC inhibition by GF109203X increased the basal PI3K activity of quiescent macrophages. The effect of the PKC inhibitor can be observed in macrophages from mice lacking class IB PI3K (p110{gamma}). Thus PKC was suggested to selectively attenuate the class IA activity. Chronic PKC activation by PMA induced PKC{delta} degradation and Akt activation. Enhancement of the basal Akt actvity was also observed in cells stably deficient in PKC{delta} prepared by shRNA technique. Fc{gamma}R-mediated phagocytosis was dramatically increased in these cells. Thus it is suggested that inactivation of class IA PI3K by PKC{delta} is functioning in regulation of Fc{gamma}R-mediated phagocytosis.

Key Words: Akt, Fc{gamma} receptor, Phagocytosis, Phosphoinositide 3-kinase, PKC{delta}

Abbreviations: PI3K, phosphoinositide 3-kinase; PKC, protein kinase C; Fc{gamma}R, Fc{gamma} Receptor; EA, IgG coated-sheep red blood cell; PMA, phorbol 12-myristate 13-acetate; LPS, lipopolysaccharide


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