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Originally published as MBC in Press, 10.1091/mbc.E08-04-0370 on August 6, 2008

Vol. 19, Issue 10, 4434-4441, October 2008

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Cyclic Guanosine Monophosphate-dependent Protein Kinase I Promotes Adhesion of Primary Vascular Smooth Muscle Cells

Pascal Weinmeister*, Robert Lukowski*, Stefan Linder{dagger}, Claudia Traidl-Hoffmann{ddagger}, Ludger Hengst§, Franz Hofmann*, and Robert Feil||

*Institut für Pharmakologie und Toxikologie, Technischen Universiät München, D-80802 München, Germany; {ddagger}ZAUM-Zentrum Allergie und Umwelt, KKG-UDA, Helmholtzzentrum München/TUM, D-80802 München, Germany; {dagger}Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten der Ludwig-Maximilians-Universität München, D-80336 München, Germany; §Sektion für Medizinische Biochemie, Medizinische Universität Innsbruck, A-6020 Innsbruck, Austria; and ||Interfakultäres Institut für Biochemie, Universität Tübingen, D-72076 Tübingen, Germany

Submitted April 9, 2008; Revised July 22, 2008; Accepted July 30, 2008
Monitoring Editor: Sandra L. Schmid

The cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase type I (cGKI) pathway regulates many cellular functions. The current study shows that 8-Br-cGMP stimulates the number of attached primary but not that of subcultured murine vascular smooth muscle cells (VSMCs). These effects of 8-Br-cGMP require the presence of cGKI. In agreement with previous studies, cGKI inhibited the number of cells in repeatedly passaged murine VSMCs. Activation of the cGMP/cGKI pathway in freshly isolated primary VSMCs slightly decreased apoptosis and strongly increased cell adhesion. The stimulation of cell adhesion by cGKI involves an inhibition of the RhoA/Rho kinase pathway and increased exposure of β1 and β3 integrins on the cell surface. Together, these results identify a novel proadhesive function of cGMP/cGKI signaling in primary VSMCs and suggest that the opposing effects of this pathway on VSMC number depend on the phenotypic context of the cells.

This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E08-04-0370) on August 6, 2008.

Address correspondence to: Pascal Weinmeister (weinmeister{at}ipt.med.tu-muenchen.de)

Abbreviations used: cAK, cAMP-dependent protein kinase; cGKI, cGMP-dependent protein kinase type I; VSMC, vascular smooth muscle cell.




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