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Autophosphorylation of the C2 domain inhibits translocation of the novel protein kinase C ( nPKC ) Apl II
Author(s) -
Farah Carole A.,
Lindeman Amanda A.,
Siu Vincent,
Gupta Micaela Das,
Sossin Wayne S.
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2012.07930.x
Subject(s) - autophosphorylation , phosphorylation , protein kinase c , microbiology and biotechnology , chromosomal translocation , biology , serine , protein kinase domain , kinase , biochemistry , protein kinase a , chemistry , mutant , gene
Protein kinase Cs (PKCs) are critical signaling molecules controlled by complex regulatory pathways. Herein, we describe an important regulatory role for C2 domain phosphorylation. Novel PKCs ( nPKC s) contain an N‐terminal C2 domain that cannot bind to calcium. Previously, we described an autophosphorylation site in the Aplysia novel PKC Apl II that increased the binding of the C2 domain to lipids. In this study, we show that the function of this phosphorylation is to inhibit PKC translocation. Indeed, a phosphomimetic serine‐glutamic acid mutation reduced translocation of PKC Apl II while blocking phosphorylation with a serine‐alanine mutation enhanced translocation and led to the persistence of the kinase at the membrane longer after the end of the stimulation. Consistent with a role for autophosphorylation in regulating kinase translocation, inhibiting PKC activity using bisindolymaleimide 1 increased physiological translocation of PKC Apl II, whereas inhibiting phosphatase activity using calyculin A inhibited physiological translocation of PKC Apl II in neurons. Our results suggest a major role for autophosphorylation‐dependent regulation of translocation.