Details

Autor(en) / Beteiligte

• Vivien, Denis
• Petitfrère, Emmanuelle
• Martiny, Laurent
• Sartelet, Hervè
• Galéra, Philippe
• Haye, Bernard
• Pujol, Jean-Pierre

Titel

IPG (inositolphosphate glycan) as a cellular signal for TGF-β1 modulation of chondrocyte cell cycle

Ist Teil von

• Journal of cellular physiology, 1993-06, Vol.155 (3), p.437-444

Ort / Verlag

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

Erscheinungsjahr

1993

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• The knowledge of transforming growth factor (TGF)‐β receptors has greatly progressed in the recent years. TGF‐β receptors type I and II have been implicated in the modulation of cell proliferation, whereas type III (betaglycan) may act as a component presenting TGF‐β to its signaling receptors. In addition, four other proteins that bind TGF‐β1 or TGF‐β2 have been recently identified in some cell lines, three being anchored to the membrane through a glycosylphosphatidylinositol (GPI). Despite this knowledge, the molecular mechanism of signal transduction through the TGF‐β receptors remain an enigma. TGF‐β family does not signal via any of the classical pathways. As GPI anchors of membrane proteins have been implicated in the transduction of some hormonal effects, we investigated the putative role of GPI in signaling the TGF‐β effects on the proliferation of rabbit articular chondrocytes (RAC). We previously showed that TGF‐β1 increased DNA replication rate of RAC, with a recruitment of cells in G2/M followed by a subsequent mitosis wave. Here, we find that the factor causes specific GPI hydrolysis, with correlated increase of inositolphosphate glycan (IPG). This effect was specifically inhibited by antibodies that bind TGF‐β1. Using [3H]‐inositol labeling and Triton X‐114 extraction, we demonstrate that a hydrophobic material from the membrane is cleaved by treatment of cell cultures with phosphatidylinositol specific phospholipase C (PI‐PLC) or by exposure to TGF‐β, supporting that a PI‐anchored molecule gives rise to IPG by TGF‐β‐induced hydrolysis. The biological relevance of this hydrolysis was demonstrated by the enhancing effect of purified IPG on the DNA synthesis rate, which mimicked the TGF‐β action. These results demonstrate that IPG could be an early messenger in the cellular signaling that mediates the effect of TGF‐β on RAC growth. © 1993 Wiley‐Liss, Inc.