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J. Biol. Chem., Vol. 277, Issue 5, 3419-3423, February 1, 2002
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From the Department of Physiology and Pharmacology, Sackler School
of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel and
Human L-type voltage-dependent
Ca2+ channels (
A Novel Long N-terminal Isoform of Human L-type Ca2+
Channel Is Up-regulated by Protein Kinase C*
, Rabin Medical Center, Petach Tikva 49100, Israel
1C, or
Cav1.2) are up-regulated by protein kinase C (PKC) in
native tissues, but in heterologous systems this modulation is absent.
In rat and rabbit, 1C has two N-terminal (NT) isoforms,
long and short, with variable initial segments of 46 and 16 amino
acids, respectively. The initial 46 amino acids of the long-NT
1C are crucial for PKC regulation. However, only a
short-NT human 1C is known. We assumed that a long-NT
isoform of human 1C may exist. By homology screening of
human genomic DNA, we identified a stretch (termed exon 1a) highly
homologous to rabbit long-NT, separated from the next known exon of
1C (exon 1b, which encodes the alternative, short-NT) by
an ~80 kb-long intron. The predicted 46-amino acid protein sequence
is highly homologous to rabbit long-NT. Reverse transcriptase PCR
showed the presence of exon 1a transcript in human cardiac RNA.
Expression of human long-NT 1C in Xenopus oocytes produced Ca2+ channel enhanced by a PKC activator,
whereas the short-NT 1C was inhibited. The long-NT
isoform may be the Ca2+ channel enhanced by PKC-activating
transmitters in human tissues.
*
This work was supported by Israel Basic Research Grant
47/00-16.0.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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