Inserm U 348 , Hopital Lariboisiere , Paris , France .
J Cell Physiol 152 : 507-19 ( 1992)
Abstract
Transforming growth factor-beta 1 ( TGF-beta 1 ) is a potent growth inhibitor for many cell types .
On fibroblasts , TGF-beta 1 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-beta 1 , which inhibited PDGF-BB mitogenicity , was able to block PDGF-BB-induced early events such as polyphosphoinositide ( PtdIns , 5-P2 , PtdIns 4-P , and PtdIns ) breakdown and Ins 1,4,5-P3 formation .
No significant modification by TGF-beta 1 of PDGF-BB binding ( n1 = 200,000 vs .
n2 = 195,000 sites per cell with TGF-beta 1 ; Kd1 = Kd2 = 0.5 x ( -9 ) M ) and of internalization kinetics was observed .
In addition , TGF-beta 1 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 .