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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

3T3 Cells

Animals

Cell Division

drug effects

Kinetics

Mice

Platelet-Derived Growth Factor

pharmacokinetics

pharmacology

Proto-Oncogene Proteins c-sis

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

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)