HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shistik, E. Articles by Ivanina, T. Search for Related Content PubMed PubMed Citation Articles by Shistik, E. Articles by Ivanina, T. Social Bookmarking                      What's this?

J Biol Chem, Vol. 274, Issue 44, 31145-31149, October 29, 1999

The N terminus of the Cardiac L-type Ca²⁺ Channel _1C Subunit
THE INITIAL SEGMENT IS UBIQUITOUS AND CRUCIAL FOR PROTEIN KINASE C MODULATION, BUT IS NOT DIRECTLY PHOSPHORYLATED

From the Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel and the ^§ Alomone Labs Ltd., P. O. Box 4287, Jerusalem 91042, Israel

The first 46 amino acids (aa) of the N terminus of the rabbit heart (RH) L-type cardiac Ca²⁺ channel _1C subunit are crucial for the stimulating action of protein kinase C (PKC) and also hinder channel gating (Shistik, E., Ivanina, T., Blumenstein, Y., and Dascal, N. (1998) J. Biol. Chem. 273, 17901-17909). The mechanism of PKC action and the location of the PKC target site are not known. Moreover, uncertainties in the genomic sequence of the N-terminal region of _1C leave open the question of the presence of RH-type N terminus in L-type channels in mammalian tissues. Here, we demonstrate the presence of _1C protein containing an RH-type initial N-terminal segment in rat heart and brain by using a newly prepared polyclonal antibody. Using deletion mutants of _1C expressed in Xenopus oocytes, we further narrowed down the part of the N terminus crucial for both inhibitory gating and for PKC effect to the first 20 amino acid residues, and we identify the first 5 aa as an important determinant of PKC action and of N-terminal effect on gating. The absence of serines and threonines in the first 5 aa and the absence of phosphorylation by PKC of a glutathione S-transferase-fusion protein containing the initial segment suggest that the effect of PKC does not arise through a direct phosphorylation of this segment. We propose that PKC acts by attenuating the inhibitory action of the N terminus via phosphorylation of a remote site, in the channel or in an auxiliary protein, that interacts with the initial segment of the N terminus.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				S. Dai, D. D. Hall, and J. W. Hell Supramolecular Assemblies and Localized Regulation of Voltage-Gated Ion Channels Physiol Rev, April 1, 2009; 89(2): 411 - 452. [Abstract] [Full Text] [PDF]

				P. J. Leary, S. Rajasekaran, R. R. Morrison, E. I. Tuomanen, T. K. Chin, and P. A. Hofmann A cardioprotective role for platelet-activating factor through NOS-dependent S-nitrosylation Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2775 - H2784. [Abstract] [Full Text] [PDF]

				H. E. D. J. ter Keurs and P. A. Boyden Calcium and Arrhythmogenesis Physiol Rev, April 1, 2007; 87(2): 457 - 506. [Abstract] [Full Text] [PDF]

				G. Baroudi, Y. Qu, O. Ramadan, M. Chahine, and M. Boutjdir Protein kinase C activation inhibits Cav1.3 calcium channel at NH2-terminal serine 81 phosphorylation site. Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1614 - H1622. [Abstract] [Full Text] [PDF]

				N. Kanevsky and N. Dascal Regulation of Maximal Open Probability Is a Separable Function of Cav{beta} Subunit in L-type Ca2+ Channel, Dependent on NH2 Terminus of {alpha}1C (Cav1.2{alpha}) J. Gen. Physiol., June 26, 2006; 128(1): 15 - 36. [Abstract] [Full Text] [PDF]

				P. Gui, X. Wu, S. Ling, S. C. Stotz, R. J. Winkfein, E. Wilson, G. E. Davis, A. P. Braun, G. W. Zamponi, and M. J. Davis Integrin Receptor Activation Triggers Converging Regulation of Cav1.2 Calcium Channels by c-Src and Protein Kinase A Pathways J. Biol. Chem., May 19, 2006; 281(20): 14015 - 14025. [Abstract] [Full Text] [PDF]

				P. Liao, T. F. Yong, M. C. Liang, D. T. Yue, and T. W. Soong Splicing for alternative structures of Cav1.2 Ca2+ channels in cardiac and smooth muscles Cardiovasc Res, November 1, 2005; 68(2): 197 - 203. [Abstract] [Full Text] [PDF]

				L. Yang, G. Liu, S. I. Zakharov, J. P. Morrow, V. O. Rybin, S. F. Steinberg, and S. O. Marx Ser1928 Is a Common Site for Cav1.2 Phosphorylation by Protein Kinase C Isoforms J. Biol. Chem., January 7, 2005; 280(1): 207 - 214. [Abstract] [Full Text] [PDF]

				M. A.G. van der Heyden, T. J.M. Wijnhoven, and T. Opthof Molecular aspects of adrenergic modulation of cardiac L-type Ca2+ channels Cardiovasc Res, January 1, 2005; 65(1): 28 - 39. [Abstract] [Full Text] [PDF]

				P. Liao, D. Yu, S. Lu, Z. Tang, M. C. Liang, S. Zeng, W. Lin, and T. W. Soong Smooth Muscle-selective Alternatively Spliced Exon Generates Functional Variation in Cav1.2 Calcium Channels J. Biol. Chem., November 26, 2004; 279(48): 50329 - 50335. [Abstract] [Full Text] [PDF]

				Z. Z. Tang, M. C. Liang, S. Lu, D. Yu, C. Y. Yu, D. T. Yue, and T. W. Soong Transcript Scanning Reveals Novel and Extensive Splice Variations in Human L-type Voltage-gated Calcium Channel, Cav1.2 {alpha}1 Subunit J. Biol. Chem., October 22, 2004; 279(43): 44335 - 44343. [Abstract] [Full Text] [PDF]

				D. H. Korzick, M. H. Laughlin, and D. K. Bowles Alterations in PKC signaling underlie enhanced myogenic tone in exercise-trained porcine coronary resistance arteries J Appl Physiol, April 1, 2004; 96(4): 1425 - 1432. [Abstract] [Full Text] [PDF]

				S. Weiss, T. Doan, K. E. Bernstein, and N. Dascal Modulation of Cardiac Ca2+ Channel by Gq-activating Neurotransmitters Reconstituted in Xenopus Oocytes J. Biol. Chem., March 26, 2004; 279(13): 12503 - 12510. [Abstract] [Full Text] [PDF]

				G. L. Kamatchi, R. Franke, C. Lynch III, and J. J. Sando Identification of Sites Responsible for Potentiation of Type 2.3 Calcium Currents by Acetyl-{beta}-methylcholine J. Biol. Chem., February 6, 2004; 279(6): 4102 - 4109. [Abstract] [Full Text] [PDF]

				C. E. Young and C. R. Yang Dopamine D1/D5 Receptor Modulates State-Dependent Switching of Soma-Dendritic Ca2+ Potentials via Differential Protein Kinase A and C Activation in Rat Prefrontal Cortical Neurons J. Neurosci., January 7, 2004; 24(1): 8 - 23. [Abstract] [Full Text] [PDF]

				L. Protas, A. Barbuti, J. Qu, V. O. Rybin, R. D. Palmiter, S. F. Steinberg, and R. B. Robinson Neuropeptide Y Is an Essential In Vivo Developmental Regulator of Cardiac ICa,L Circ. Res., November 14, 2003; 93(10): 972 - 979. [Abstract] [Full Text] [PDF]

				Z. Lin, P.-W. Zhang, X. Zhu, J.-M. Melgari, R. Huff, R. L. Spieldoch, and G. R. Uhl Phosphatidylinositol 3-Kinase, Protein Kinase C, and MEK1/2 Kinase Regulation of Dopamine Transporters (DAT) Require N-terminal DAT Phosphoacceptor Sites J. Biol. Chem., May 23, 2003; 278(22): 20162 - 20170. [Abstract] [Full Text] [PDF]

				K. B Walsh and G. E Parks Changes in cardiac myocyte morphology alter the properties of voltage-gated ion channels Cardiovasc Res, July 1, 2002; 55(1): 64 - 75. [Abstract] [Full Text] [PDF]

				Y. Blumenstein, N. Kanevsky, G. Sahar, R. Barzilai, T. Ivanina, and N. Dascal A Novel Long N-terminal Isoform of Human L-type Ca2+ Channel Is Up-regulated by Protein Kinase C J. Biol. Chem., January 25, 2002; 277(5): 3419 - 3423. [Abstract] [Full Text] [PDF]

				K. D. Keef, J. R. Hume, and J. Zhong Regulation of cardiac and smooth muscle Ca2+ channels (CaV1.2a,b) by protein kinases Am J Physiol Cell Physiol, December 1, 2001; 281(6): C1743 - C1756. [Abstract] [Full Text] [PDF]

				M. J. Davis, X. Wu, T. R. Nurkiewicz, J. Kawasaki, P. Gui, M. A. Hill, and E. Wilson Regulation of ion channels by protein tyrosine phosphorylation Am J Physiol Heart Circ Physiol, November 1, 2001; 281(5): H1835 - H1862. [Abstract] [Full Text] [PDF]

				D. McHugh, E. M. Sharp, T. Scheuer, and W. A. Catterall Inhibition of cardiac L-type calcium channels by protein kinase C phosphorylation of two sites in the N-terminal domain PNAS, October 12, 2000; (2000) 210384297. [Abstract] [Full Text]

				T. Ivanina, Y. Blumenstein, E. Shistik, R. Barzilai, and N. Dascal Modulation of L-type Ca2+ Channels by Gbeta gamma and Calmodulin via Interactions with N and C Termini of alpha 1C J. Biol. Chem., December 15, 2000; 275(51): 39846 - 39854. [Abstract] [Full Text] [PDF]

				D. McHugh, E. M. Sharp, T. Scheuer, and W. A. Catterall Inhibition of cardiac L-type calcium channels by protein kinase C phosphorylation of two sites in the N-terminal domain PNAS, October 24, 2000; 97(22): 12334 - 12338. [Abstract] [Full Text] [PDF]

				K. J. Alden, P. H. Goldspink, S. W. Ruch, P. M. Buttrick, and J. Garcia Enhancement of L-type Ca2+ current from neonatal mouse ventricular myocytes by constitutively active PKC-beta II Am J Physiol Cell Physiol, April 1, 2002; 282(4): C768 - C774. [Abstract] [Full Text] [PDF]