An inositolphosphate glycan released by TGF-beta mimics the proliferative but not the transcriptional effects of the factor and requires functional receptors.
Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional polypeptide that regulates a number of cellular processes including cell growth and deposition of extracellular matrix protein. Despite the fact that the signal transduction by TGF-beta has been intensively studied, the molecular mechanisms of that pathway are not clear. We have studied the possibility that an inositolphosphate glycan (IPG) is involved in transmission of the TGF-beta 1 signal. We show that TGF-beta 1 induces IPG release in both rabbit articular chondrocytes (RAC), which are growth stimulated by the factor and Mv1Lu cell line, which is growth inhibited. This release requires functional TGF-beta heteromeric receptors in these two cell types. We also demonstrate that IPG mimics TGF-beta 1-induced growth stimulation in mesenchymal cells (+100%) and growth inhibition in epithelial cells (-80%). Moreover TGF-beta receptor I (T beta R-I) is not required for inhibition of proliferation induced by IPG since derivated mutants of the Mv1Lu cell line lacking T beta R-I intracellular domain (R-1B) are significantly inhibited (-65%). Additionally, we show that IPG does not take part in the signalling pathway that leads to activation of matrix gene transcription. These results suggest that TGF-beta effects on growth regulation and extracellular matrix synthesis implicate two different signalling pathways, IPG being only involved in growth regulation.
Bogdanowicz
P
P
Laboratoire de Biochimie du Tissu Conjonctif, Faculté de Médecine, Caen, France.
Vivien
D
D
Felisaz
N
N
Léon
V
V
Pujol
J P
JP
D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology; D002455:Cell Division; D002460:Cell Line; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D007295:Inositol Phosphates / Q000378:metabolism* / Q000494:pharmacology; D008907:Mink; D018716:Molecular Mimicry; D011134:Polysaccharides / Q000378:metabolism* / Q000494:pharmacology; D011817:Rabbits; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D007295:Inositol Phosphates; D011134:Polysaccharides; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; C028039:inositol phosphate glycan; D004247:DNA