TNF-alpha suppresses the PDGF beta-receptor kinase

Summary, in English

PDGF and TNF-alpha are both known to play important roles in inflammation, albeit frequently by opposing actions. Typically, TNF-alpha can attenuate PDGF beta-receptor signaling. Pretreatment of mouse 3T3 L1 fibroblasts with TNF-alpha greatly diminished their proliferative response to PDGF. However, TNF-alpha affected neither the binding of PDGF-BB to cell surface receptors nor the total amount of PDGF beta-receptor in the cells, but decreased the PDGF-induced in vitro kinase activity of the receptor. The phosphatase inhibitor ortho-vanadate did not prevent this effect. Ortho-phosphate labeling of cells prior to TNF-alpha treatment and PDGF-BB stimulation confirmed a decrease of in vivo phosphorylation of the PDGF beta-receptor. Two-dimensional mapping after tryptic cleavage as well as phosphoamino acid analysis demonstrated a general decrease in phosphorylation of all known tyrosine residues in the PDGF beta-receptor. The exact mechanism for this suppression remains to be clarified

• Author: Catrin Molander; Anders Kallin; H Izumi; Lars Rönnstrand; Keiko Funa
• Publishing year: 2000
• Language: English
• Pages: 65-71
• Publication/Series: Experimental Cell Research
• Volume: 258
• Issue: 1
• Links: http://dx.doi.org/10.1006/excr.2000.4917
• Document type: Journal article
• Publisher: Academic Press
• Topic: Medicinal Chemistry
• Keywords: 3T3 Cells Animals Cell Division/drug effects Kinetics Mice Platelet-Derived Growth Factor/pharmacokinetics/*pharmacology Receptor Protein-Tyrosine Kinases/*antagonists & inhibitors Receptor; Platelet-Derived Growth Factor beta/drug effects/*physiology Signal Transduction/drug effects Transforming Growth Factor beta/*pharmacology Vanadates/pharmacology
• Status: Published
• ISBN/ISSN/Other: ISSN: 1090-2422