Differential stimulation of PKC phosphorylation of potassium channels by ZIP1 and ZIP2.
Targeting of protein modification enzymes is a key biochemical step to achieve specific and effective posttranslational modifications. Two alternatively spliced ZIP1 and ZIP2 proteins are described, which bind to both Kvbeta2 subunits of potassium channel and protein kinase C (PKC) zeta, thereby acting as a physical link in the assembly of PKCzeta-ZIP-potassium channel complexes. ZIP1 and ZIP2 differentially stimulate phosphorylation of Kvbeta2 by PKCzeta. They also interact to form heteromultimers, which allows for a hybrid stimulatory activity to PKCzeta. Finally, ZIP1 and ZIP2 coexist in the same cell type and are elevated differentially by neurotrophic factors. These results provide a mechanism for specificity and regulation of PKCzeta-targeted phosphorylation.
Gong
J
J
Department of Physiology, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Xu
J
J
Bezanilla
M
M
van Huizen
R
R
Derin
R
R
Li
M
M
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002531:Cerebellum / Q000378:metabolism; D018076:DNA, Complementary; D007527:Isoenzymes / Q000378:metabolism; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D015221:Potassium Channels / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D014162:Transfection; D000099221:Protein Kinase C zeta
D002352:Carrier Proteins; D018076:DNA, Complementary; D007527:Isoenzymes; D004676:Myelin Basic Protein; D009414:Nerve Growth Factors; D015221:Potassium Channels; D011493:Protein Kinase C; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D000099221:Protein Kinase C zeta