Intracellular signaling pathways required for rat vascular smooth muscle cell migration. Interactions between basic fibroblast growth factor and platelet-derived growth factor

Intracellular signaling pathways activated by both PDGF and basic fibroblast growth factor (bFGF) have been implicated in the migration of vascular smooth muscle cells (VSMC), a key step in the pathogenesis of many vascular diseases. We demonstrate here that, while bFGF is a weak chemoattractant for...

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Bibliographic Details
Published inThe Journal of clinical investigation Vol. 96; no. 4; pp. 1905 - 1915
Main Authors Bilato, C, Pauly, R R, Melillo, G, Monticone, R, Gorelick-Feldman, D, Gluzband, Y A, Sollott, S J, Ziman, B, Lakatta, E G, Crow, M T
Format Journal Article
LanguageEnglish
Published United States 01.10.1995
Subjects
Animals
Calcium - metabolism
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
Cell Movement
Cells, Cultured
Fibroblast Growth Factor 2 - physiology
Humans
Mice
Muscle, Smooth, Vascular - cytology
Platelet-Derived Growth Factor - physiology
Rats
Rats, Wistar
RNA, Messenger - analysis
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Summary:Intracellular signaling pathways activated by both PDGF and basic fibroblast growth factor (bFGF) have been implicated in the migration of vascular smooth muscle cells (VSMC), a key step in the pathogenesis of many vascular diseases. We demonstrate here that, while bFGF is a weak chemoattractant for VSMCs, it is required for the PDGF-directed migration of VSMCs and the activation of calcium/calmodulin-dependent protein kinase II (CamKinase II), an intracellular event that we have previously shown to be important in the regulation of VSMC migration. Neutralizing antibodies to bFGF caused a dramatic reduction in the size of the intracellular calcium transient normally seen after PDGF stimulation and inhibited both PDGF-directed VSMC migration and CamKinase II activation. Partially restoring the calcium transient with ionomycin restored migration and CamKinase II activation as did the forced expression of a mutant CamKinase II that had been "locked" in the active state by site-directed mutagenesis. These results suggest that bFGF links PDGF receptor stimulation to changes in intracellular calcium and CamKinase II activation, reinforcing the central role played by CamKinase II in regulating VSMC migration.
ISSN:0021-9738
DOI:10.1172/jci118236