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) All Versions of this Article: 289/5/C1343    most recent 00064.2005v2 00064.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Lu, K. K. Articles by Singer, H. A. Search for Related Content PubMed PubMed Citation Articles by Lu, K. K. Articles by Singer, H. A.

REPORT

RECEPTORS AND SIGNAL TRANSDUCTION

Adhesion-dependent activation of CaMKII and regulation of ERK activation in vascular smooth muscle

Center for Cardiovascular Sciences, Albany Medical College, Albany, New York

Submitted 14 February 2005 ; accepted in final form 2 June 2005

ABSTRACT

Cell adhesion-dependent activation of ERK1/2 has been linked functionally to focal adhesion dynamics. We previously reported that in adherent vascular smooth muscle (VSM) cells, CaMKII mediates ERK1/2 activation in response to Ca²⁺-mobilizing stimuli. In the present study, we tested whether CaMKII regulates ERK1/2 signaling in response to VSM cell adhesion. Using an antibody that specifically recognizes CaMKII autophosphorylated on Thr²⁸⁷, we determined that CaMKII is rapidly activated (within 1 min) after the adherence of cells on multiple ECM substrates. Activation of CaMKII on fibronectin was unaffected in cells overexpressing focal adhesion kinase (FAK)-related nonkinase (FRNK), an endogenous inhibitor of FAK. Furthermore, CaMKII was rapidly and robustly activated in VSM cells plated on poly-L-lysine. These results suggest that adhesion-dependent CaMKII activation is integrin independent. Adhesion-dependent FAK activation on fibronectin was not affected in cells treated with the selective CaMKII inhibitor KN-93 (30 µM) or in cells in which the expression of CaMKII with small interfering RNA (siRNA) was suppressed, although tyrosine phosphorylation of paxillin was inhibited in CaMKII-₂-suppressed cells. Sustained ERK1/2 activation that was dependent on FAK activation (inhibited by FRNK) was also attenuated by CaMKII inhibition or siRNA-mediated gene silencing. Rapid ERK1/2 activation that preceded FAK and paxillin activation was detected upon VSM cell adhesion to poly-L-lysine, and this response was inhibited by CaMKII gene silencing. These results indicate that integrin-independent CaMKII activation is an early signal during VSM cell adhesion that positively modulates ERK1/2 signaling through FAK-dependent and FAK-independent mechanisms.

calcium/calmodulin-dependent protein kinase II; cell adhesion; extracellular signal-regulated protein kinases; paxillin; focal adhesion kinase

This article has been cited by other articles:

				M. Z. Mercure, R. Ginnan, and H. A. Singer CaM kinase II{delta}2-dependent regulation of vascular smooth muscle cell polarization and migration Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1465 - C1475. [Abstract] [Full Text] [PDF]

				S. J. House and H. A. Singer CaMKII-{delta} Isoform Regulation of Neointima Formation After Vascular Injury Arterioscler. Thromb. Vasc. Biol., March 1, 2008; 28(3): 441 - 447. [Abstract] [Full Text] [PDF]

				S. J. House, R. G. Ginnan, S. E. Armstrong, and H. A. Singer Calcium/calmodulin-dependent protein kinase II-{delta} isoform regulation of vascular smooth muscle cell proliferation Am J Physiol Cell Physiol, June 1, 2007; 292(6): C2276 - C2287. [Abstract] [Full Text] [PDF]

				R. J. Jones, D. Jourd'heuil, J. C. Salerno, S. M. E. Smith, and H. A. Singer iNOS regulation by calcium/calmodulin-dependent protein kinase II in vascular smooth muscle Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2634 - H2642. [Abstract] [Full Text] [PDF]

				P. J. Pagano and M. J. Haurani Vascular Cell Locomotion: Osteopontin, NADPH Oxidase, and Matrix Metalloproteinase-9 Circ. Res., June 23, 2006; 98(12): 1453 - 1455. [Full Text] [PDF]