The regulation of caveolin expression and localization by serum and heparin in vascular smooth muscle cells.
Caveolae have been implicated in growth factor receptor and G-protein coupled receptor signaling in vascular cells. It has been postulated that caveolin, the structural protein of caveolae, may act as a general tyrosine kinase inhibitor by binding and inhibiting signaling molecules involved in the activation of the MAP kinase proliferation cascade. Using an in vitro model of VSMC proliferation, we found that serum stimulation caused a dose dependent decrease in both caveolin-1 and caveolin-2 protein levels in human coronary artery smooth muscle cells. Heparin, an inhibitor of VSMC proliferation, inhibited the serum-induced loss of caveolin-1 and caveolin-2. In addition, heparin caused an increase in both caveolin-1 and caveolin-2 localization to caveolae-enriched sucrose gradient membrane fractions when compared to serum alone. Taken together, caveolin may play an important role in the regulation of VSMC proliferation and heparin and serum have opposing effects on caveolin expression and localization in VSMC.
Peterson
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TE
Divisions of Cardiovascular Diseases and Biochemistry and Molecular Biology and Molecular Medicine Program, Mayo Clinic and Foundation, Rochester, Minnesota, 55905, USA.
Kleppe
L S
LS
Caplice
N M
NM
Pan
S
S
Mueske
C S
CS
Simari
R D
RD
D051242:Caveolin 1; D051243:Caveolin 2; D022461:Caveolins; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
C495540:CAV1 protein, human; D051242:Caveolin 1; D051243:Caveolin 2; D022461:Caveolins; D003470:Culture Media; D008565:Membrane Proteins; D006493:Heparin