Cyclic guanosine monophosphate-dependent protein kinase I promotes adhesion of primary vascular smooth muscle cells.
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 beta(1) and beta(3) 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.
Weinmeister
Pascal
P
Institut für Pharmakologie und Toxikologie, Technischen Universiät München, D-80802 München, Germany. weinmeister@ipt.med.tu-muenchen.de
Lukowski
Robert
R
Linder
Stefan
S
Traidl-Hoffmann
Claudia
C
Hengst
Ludger
L
Hofmann
Franz
F
Feil
Robert
R
D000818:Animals; D001011:Aorta / Q000378:metabolism; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D019012:Integrin beta1 / Q000378:metabolism; D039661:Integrin beta3 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D013347:Subcellular Fractions
D019012:Integrin beta1; D039661:Integrin beta3; D047908:Intracellular Signaling Peptides and Proteins; C015482:protein kinase modulator; C016276:8-bromocyclic GMP; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP