A PKC epsilon-ENH-channel complex specifically modulates N-type Ca2+ channels.
Multiple protein kinase C (PKC) isozymes are present in neurons, where they regulate a variety of cellular functions. Due to the lack of specific PKC isozyme inhibitors, it remains unknown how PKC acts on its selective target(s) and achieves its specific actions. Here we show that a PKC binding protein, enigma homolog (ENH), interacts specifically with both PKCepsilon and N-type Ca2+ channels, forming a PKCepsilon-ENH-Ca2+ channel macromolecular complex. Coexpression of ENH facilitated modulation of N-type Ca2+ channel activity by PKC. Disruption of the complex reduced the potentiation of the channel activity by PKC in neurons. Thus, ENH, by interacting specifically with both PKCepsilon and the N-type Ca2+ channel, targets a specific PKC to its substrate to form a functional signaling complex, which is the molecular mechanism for the specificity and efficiency of PKC signaling.
Maeno-Hikichi
Yuka
Y
Department of Pharmacology, University of Pennsylvania School of Medicine, 3620 Hamilton Walk, Philadelphia, Pennsylvania 19104, USA.
Chang
Shaohua
S
Matsumura
Kiyoyuki
K
Lai
Meizan
M
Lin
Hong
H
Nakagawa
Noritaka
N
Kuroda
Shun'ichi
S
Zhang
Ji-fang
JF
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D005260:Female; D015723:Gene Library; D007527:Isoenzymes / Q000378:metabolism; D046911:Macromolecular Substances; D009474:Neurons / Q000378:metabolism; D009865:Oocytes; D011485:Protein Binding / Q000502:physiology; D020033:Protein Isoforms / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology*; D051744:Protein Kinase C-epsilon; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D014982:Xenopus laevis
D048868:Adaptor Proteins, Signal Transducing; D020864:Calcium Channels, N-Type; D002352:Carrier Proteins; D007527:Isoenzymes; D046911:Macromolecular Substances; C102578:Pdlim5 protein, rat; D020033:Protein Isoforms; C497257:Prkce protein, rat; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon