Differential phosphorylation of two size forms of the neuronal class C L-type calcium channel α1 subunit

Johannes W Hell, Charles T. Yokoyama, Scott T. Wong, Concepcion Warner, Terry P. Snutch, William A. Catterall

Research output: Contribution to journalArticle

149 Scopus citations

Abstract

L-type calcium channels mediate long-lasting calcium currents which are modulated by protein phosphorylation. Using site-directed anti-peptide antibodies, we show that the al subunit of the neuronal class C L-type calcium channel from rat brain exists in two size forms. The longer form, LC2, with an apparent molecular mass of 210-235 kDa was phosphorylated in vitro by cAMP-dependent'protein kinase (cA-PK), but the shorter form, LC1, with an apparent molecular mass of 190-195 kDa was not a substrate for cA-PK. In contrast, LC1 and LC2 are both substrates for protein kinase C (PKC), calcium- and calmodulin-dependent protein kinase II, and cGMP-dependent protein kinase (cG-PK). The site-directed anti-peptide antibody CNC2 was produced against the COOH-terminal end of the class C L-type α1 subunit as predicted by molecular cloning and sequencing of cDNA. CNC2 recognized LC2 but not LC1 by immunoblotting and immunoprecipitated only LC2 phosphorylated by either cA-PK or PKC. These results indicate that LC1 is truncated at its COOH-terminal end with respect to LC2 and that cA-PK preferentially phosphorylates sites in the COOH-terminal region of the al subunit that are present in Lc2 but not LC1. The selectivity of cA-PK for phosphorylation of the COOH-terminal region of LC2 suggests that the channel activities of the two α1 subunit size forms may be differentially regulated by neurotransmitters and hormones which act through cAMP-dependent mechanisms, while both α1 subunit isoforms may be modulated by PKC, cG-PK, and calcium- and calmodulin-dependent protein kinase II.

Original languageEnglish (US)
Pages (from-to)19451-19457
Number of pages7
JournalJournal of Biological Chemistry
Volume268
Issue number26
StatePublished - Sep 15 1993
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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    Hell, J. W., Yokoyama, C. T., Wong, S. T., Warner, C., Snutch, T. P., & Catterall, W. A. (1993). Differential phosphorylation of two size forms of the neuronal class C L-type calcium channel α1 subunit. Journal of Biological Chemistry, 268(26), 19451-19457.