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Tumor necrosis factor receptors (Tnfr) in mouse fibroblasts deficient in Tnfr1 or Tnfr2 are signaling competent and activate the mitogen-activated protein kinase pathway with differential kinetics.
J Biol Chem. 1996 Nov 08; 271(45):28097-104.JB

Abstract

To dissect tumor necrosis factor receptor (Tnfr)-1 (CD120a) and Tnfr2 (CD120b)-dependent signal transduction pathways, primary fibroblasts isolated from inguinal adipose tissue of wild type (wt), tnfr1(o), tnfr2(o), and tnfr1(o)/tnfr2(o) mice were studied. The mitogen-activated protein kinases Erk1 and Erk2 were found to be tyrosine-phosphorylated and activated by Tnf treatment in all wt, tnfr1(o), and tnfr2(o) fibroblasts; the activation was down-regulated 60 min after the start of steady state Tnf treatment. Distinct kinetics of Erk1 and Erk2 activation were detected; the Tnfr1-mediated activation of Erk1 and Erk2 started more slowly and persisted for more prolonged times as compared with Tnfr2 activation. Raf-1, Raf-B, Mek-1, Mek kinase, and p90(rsk) kinases were also shown to be activated independently in a distinct time-dependent pattern through the two Tnf receptors. In addition, both Tnfr1 and Tnfr2 mediated independently the activation of the transcription factor Ap-1 albeit with parallel activation kinetics. In contrast, Tnfr1 exclusively mediated activation of NF-kappaB and fibroblast proliferation; however, Tnfr2 enhanced proliferation triggered through Tnfr1. These findings indicate distinct but also overlapping roles of Tnfr1 and Tnfr2 in primary mouse fibroblasts and suggest different regulation mechanisms of signal transduction pathways under the control of both Tnf receptors.

Authors+Show Affiliations

Department of Nervous System Diseases PRPN, F. Hoffmann-La Roche, 4070 Basel, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

8910423

Citation

Kalb, A, et al. "Tumor Necrosis Factor Receptors (Tnfr) in Mouse Fibroblasts Deficient in Tnfr1 or Tnfr2 Are Signaling Competent and Activate the Mitogen-activated Protein Kinase Pathway With Differential Kinetics." The Journal of Biological Chemistry, vol. 271, no. 45, 1996, pp. 28097-104.
Kalb A, Bluethmann H, Moore MW, et al. Tumor necrosis factor receptors (Tnfr) in mouse fibroblasts deficient in Tnfr1 or Tnfr2 are signaling competent and activate the mitogen-activated protein kinase pathway with differential kinetics. J Biol Chem. 1996;271(45):28097-104.
Kalb, A., Bluethmann, H., Moore, M. W., & Lesslauer, W. (1996). Tumor necrosis factor receptors (Tnfr) in mouse fibroblasts deficient in Tnfr1 or Tnfr2 are signaling competent and activate the mitogen-activated protein kinase pathway with differential kinetics. The Journal of Biological Chemistry, 271(45), 28097-104.
Kalb A, et al. Tumor Necrosis Factor Receptors (Tnfr) in Mouse Fibroblasts Deficient in Tnfr1 or Tnfr2 Are Signaling Competent and Activate the Mitogen-activated Protein Kinase Pathway With Differential Kinetics. J Biol Chem. 1996 Nov 8;271(45):28097-104. PubMed PMID: 8910423.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tumor necrosis factor receptors (Tnfr) in mouse fibroblasts deficient in Tnfr1 or Tnfr2 are signaling competent and activate the mitogen-activated protein kinase pathway with differential kinetics. AU - Kalb,A, AU - Bluethmann,H, AU - Moore,M W, AU - Lesslauer,W, PY - 1996/11/8/pubmed PY - 1996/11/8/medline PY - 1996/11/8/entrez SP - 28097 EP - 104 JF - The Journal of biological chemistry JO - J Biol Chem VL - 271 IS - 45 N2 - To dissect tumor necrosis factor receptor (Tnfr)-1 (CD120a) and Tnfr2 (CD120b)-dependent signal transduction pathways, primary fibroblasts isolated from inguinal adipose tissue of wild type (wt), tnfr1(o), tnfr2(o), and tnfr1(o)/tnfr2(o) mice were studied. The mitogen-activated protein kinases Erk1 and Erk2 were found to be tyrosine-phosphorylated and activated by Tnf treatment in all wt, tnfr1(o), and tnfr2(o) fibroblasts; the activation was down-regulated 60 min after the start of steady state Tnf treatment. Distinct kinetics of Erk1 and Erk2 activation were detected; the Tnfr1-mediated activation of Erk1 and Erk2 started more slowly and persisted for more prolonged times as compared with Tnfr2 activation. Raf-1, Raf-B, Mek-1, Mek kinase, and p90(rsk) kinases were also shown to be activated independently in a distinct time-dependent pattern through the two Tnf receptors. In addition, both Tnfr1 and Tnfr2 mediated independently the activation of the transcription factor Ap-1 albeit with parallel activation kinetics. In contrast, Tnfr1 exclusively mediated activation of NF-kappaB and fibroblast proliferation; however, Tnfr2 enhanced proliferation triggered through Tnfr1. These findings indicate distinct but also overlapping roles of Tnfr1 and Tnfr2 in primary mouse fibroblasts and suggest different regulation mechanisms of signal transduction pathways under the control of both Tnf receptors. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/8910423/Tumor_necrosis_factor_receptors__Tnfr__in_mouse_fibroblasts_deficient_in_Tnfr1_or_Tnfr2_are_signaling_competent_and_activate_the_mitogen_activated_protein_kinase_pathway_with_differential_kinetics_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(18)35119-6 DB - PRIME DP - Unbound Medicine ER -