Responses of pertussis toxin-treated microvascular endothelial cells to transforming growth factor beta 1. No evidence for pertussis-sensitive G-protein involvement in TGF-beta signal transduction.

Abstract

Responses of bovine adrenal capillary endothelial cells (BACE) on treatment with transforming growth factor beta 1 (TGF-beta 1) have been characterized and tested for sensitivity to inactivation of pertussis toxin-sensitive G-proteins. TGF-beta 1 elicited growth inhibition, monolayer remodeling, elevation of steady state mRNA levels for collagen type 1 (alpha 1(1) and alpha 2(1)) and TGF-beta 1, and inhibition of p34cdc2 histone H1 kinase activity in BACE cells. Pertussis toxin treatment enhanced both inhibition of BACE cell [3H]methylthymidine uptake and remodeling of BACE monolayers by TGF-beta 1. These findings contrast with studies of mink lung epithelial cells, in which TGF-beta 1 growth inhibition has been shown to be pertussis-sensitive. Further investigation revealed that pertussis toxin treatment of BACE cells had no effect on TGF-beta 1-stimulated elevation of steady state mRNA levels for collagen type 1 (alpha 1(1) or alpha 2(1)) or for TGF-beta 1. Analysis of p34cdc2 activity in BACE cells revealed potent inhibition of p34cdc2 histone H1 kinase activity by TGF-beta 1. Pertussis toxin treatment also abolished the increase in p34cdc2 activity, however, precluding the determination of the pertussis toxin sensitivity of this response to TGF-beta 1. Consistent with suppression of p34cdc2 activation, pertussis toxin also caused substantial inhibition of mitogen-stimulated BACE cell [3H]methylthymidine uptake. It is concluded that TGF-beta 1 signal transduction in this cell type does not involve G-proteins of the pertussis toxin-sensitive class and that, in view of its potent effects on DNA synthesis and p34cdc2 activation, the use of pertussis toxin to determine G-protein involvement in cytokine signalling pathways should be approached with caution.

• Authors: S A McCarthy, R Bicknell
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 267 Issue 30 Pg. 21617-22 (Oct 25 1992) ISSN: 0021-9258 [Print] United States
• PMID: 1328241 (Publication Type: Journal Article)

Chemical References

• RNA, Messenger
• Transforming Growth Factor beta
• Virulence Factors, Bordetella
• Collagen
• methylthymidine
• Pertussis Toxin
• Protamine Kinase
• CDC2 Protein Kinase
• GTP-Binding Proteins
• Thymidine

Topics

• Animals
• CDC2 Protein Kinase (metabolism)
• Cattle
• Cell Membrane (metabolism)
• Cells, Cultured
• Collagen (genetics)
• Endothelium, Vascular (drug effects, enzymology, metabolism)
• GTP-Binding Proteins (metabolism)
• Gene Expression Regulation
• Pertussis Toxin
• Precipitin Tests
• Protamine Kinase (metabolism)
• RNA, Messenger (genetics)
• Signal Transduction
• Thymidine (analogs & derivatives, metabolism)
• Transforming Growth Factor beta (genetics, pharmacology)
• Virulence Factors, Bordetella (pharmacology)