ISSN:
0021-9541
Keywords:
Life and Medical Sciences
;
Cell & Developmental Biology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Biology
,
Medicine
Notes:
Transforming growth factor-β1 (TGF-β1) is a potent growth inhibitor for many cell types. On fibroblasts, TGF-β1 has been shown to inhibit human platelet-derived growth factor (PDGF)-induced mitogenicity. The mechanism implicated in this growth inhibition is unknown. In this work, we show on human bone marrow fibroblasts that TGF-β1, which inhibited PDGF-BB mitogenicity, was able to block PDGF-BB-induced early events such as polyphosphoinositide (Ptdlns 4,5-P2, Ptdlns 4-P, and Ptdlns) breakdown and Ins 1,4,5-P3 formation. No significant modification by TGF-β1 of PDGF-BB binding (n1 = 200,000 vs. n2 = 195,000 sites per cell with TGF-β1; Kd1 = Kd2 = 0.5 × 10-9M) and of internalization kinetics was observed. In addition, TGF-β1 was shown to inhibit PDGF-BB receptor autophosphorylation either in intact cells or in partially isolated membranes and to partially inhibit PDGF-R tyrosine kinase activity. Since a dephosphorylation mechanism through protein phosphatases could be implicated, we used okadaic acid, a potent inhibitor of type 1 and 2A serine/threonine phosphatases and showed that okadaic acid restored PDGF-receptor autophosphorylation on tyrosine residues. Based on these data, we suggest that an alternative regulatory mechanism of PDGF tyrosine phosphorylation seems to involve serine/threonine phosphatase activation. © 1992 Wiley-Liss, Inc.
Additional Material:
10 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jcp.1041520310
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