TY - JOUR
T1 - Intracellular signaling pathways required for rat vascular smooth muscle cell migration
T2 - Interactions between basic fibroblast growth factor and platelet-derived growth factor
AU - Bilato, Claudio
AU - Pauly, Rebecca R.
AU - Melillo, Guido
AU - Monticone, Robert
AU - Gorelick-Feldman, Dan
AU - Gluzband, Yehezkiel A.
AU - Sollott, Steven J.
AU - Ziman, Bruce
AU - Lakatta, Edward G.
AU - Crow, Michael T.
PY - 1995/10
Y1 - 1995/10
N2 - 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.
AB - 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.
KW - Basic fibroblast growth factor
KW - Calcium/calmodulin-dependent kinase II
KW - Cell migration
KW - Platelet-derived growth factor
KW - Smooth muscle cells
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M3 - Article
C2 - 7560082
AN - SCOPUS:0028810992
SN - 0021-9738
VL - 96
SP - 1905
EP - 1915
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 4
ER -