TY - JOUR
T1 - Decreased PDGF receptor kinase activity in fibroblasts contracting stressed collagen matrices
AU - Lin, Ying Chun
AU - Ho, Chin Han
AU - Grinnell, Frederick
N1 - Funding Information:
We are indebted to Dr. Carl-Henrik Heldin for providing antibodies against the PDGF receptor and assisting us with the PDGF receptor kinase assay and to Joseph Albanesi, William Snell, and Michael White for their helpful comments. These studies were supported by a grant from the NIH, GM31321.
PY - 1998/5/1
Y1 - 1998/5/1
N2 - Fibroblasts cultured in mechanically stressed collagen matrices proliferate, whereas cells in floating collagen matrices become quiescent. Previous research indicated that one factor contributing to cell quiescence in floating matrices was reduced receptor autophosphorylation in response to PDGF stimulation (i.e., PDGF receptor desensitization). To learn more about the mechanism of PDGF receptor desensitization, we analyzed changes in PDGF receptor autophosphorylation and receptor kinase activity after stressed collagen matrices were switched to floating conditions, which results in rapid cell contraction and dissipation of mechanical stress. PDGF receptor desensitization occurred during contraction stimulated by serum but not in the absence of serum, and desensitization was prevented by inhibitors of contraction but not by inhibitors of the contraction-activated cyclic AMP signaling pathway. Receptor desensitization resulted from decreased receptor kinase activity rather than from elevated protein tyrosine phosphatase activity, and only receptors unoccupied at the time of contraction were affected. After contraction, radiolabeled PDGF binding to the cells was decreased, which suggested that receptor desensitization resulted from a contraction-dependent change in receptor availability or affinity.
AB - Fibroblasts cultured in mechanically stressed collagen matrices proliferate, whereas cells in floating collagen matrices become quiescent. Previous research indicated that one factor contributing to cell quiescence in floating matrices was reduced receptor autophosphorylation in response to PDGF stimulation (i.e., PDGF receptor desensitization). To learn more about the mechanism of PDGF receptor desensitization, we analyzed changes in PDGF receptor autophosphorylation and receptor kinase activity after stressed collagen matrices were switched to floating conditions, which results in rapid cell contraction and dissipation of mechanical stress. PDGF receptor desensitization occurred during contraction stimulated by serum but not in the absence of serum, and desensitization was prevented by inhibitors of contraction but not by inhibitors of the contraction-activated cyclic AMP signaling pathway. Receptor desensitization resulted from decreased receptor kinase activity rather than from elevated protein tyrosine phosphatase activity, and only receptors unoccupied at the time of contraction were affected. After contraction, radiolabeled PDGF binding to the cells was decreased, which suggested that receptor desensitization resulted from a contraction-dependent change in receptor availability or affinity.
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U2 - 10.1006/excr.1998.4013
DO - 10.1006/excr.1998.4013
M3 - Article
C2 - 9597011
AN - SCOPUS:0031853066
SN - 0014-4827
VL - 240
SP - 377
EP - 387
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 2
ER -