TNF-alpha suppresses the PDGF beta-receptor kinase.
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.
Department of Anatomy and Cell Biology, Göteborg University, Gothenburg, Sweden.
C
C
Molander
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Kallin
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H
Izumi
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Rönnstrand
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K
Funa
D016475:3T3 Cells; D000818:Animals; D000077214:Becaplermin; D002455:Cell Division / Q000187:drug effects; D007700:Kinetics; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000493:pharmacokinetics / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014638:Vanadates / Q000494:pharmacology
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D016212:Transforming Growth Factor beta; D000077214:Becaplermin; D014638:Vanadates; D020794:Receptor Protein-Tyrosine Kinases; D020797:Receptor, Platelet-Derived Growth Factor beta