PMID- 9405407 OWN - NLM STAT- MEDLINE DCOM- 19980122 LR - 20211203 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 272 IP - 51 DP - 1997 Dec 19 TI - Activation of stress-activated protein kinase/c-Jun N-terminal kinase, but not NF-kappaB, by the tumor necrosis factor (TNF) receptor 1 through a TNF receptor-associated factor 2- and germinal center kinase related-dependent pathway. PG - 32102-7 AB - A key step by which tumor necrosis factor (TNF) signals the activation of nuclear factor-kappaB (NF-kappaB) and the stress-activated protein kinase (SAPK, also called c-Jun N-terminal kinase or JNK) is the recruitment to the TNF receptor of TNF receptor-associated factor 2 (TRAF2). However, the subsequent steps in TRAF2-induced SAPK and NF-kappaB activation remain unresolved. Here we report the identification of a TNF-responsive serine/threonine protein kinase termed GCK related (GCKR) that likely signals via mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase kinase 1 (MEKK1) to activate the SAPK pathway. TNF, TRAF2, and ultraviolet (UV) light, which in part uses the TNF receptor signaling pathway, all increased GCKR activity. A TRAF2 mutant, which inhibits both TRAF2-induced NF-kappaB and SAPK activation, blocked TNF-induced GCKR activation. Finally, interference with GCKR expression impeded TRAF2- and TNF-induced SAPK activation but not that of NF-kappaB. This suggests a divergence in the TNF signaling pathway that leads to SAPK and NF-kappaB activation, which is located downstream of TRAF2 but upstream of GCKR. FAU - Shi, C S AU - Shi CS AD - B Cell Molecular Immunology Section, Laboratory of Immunoregulation, NIAID, National Institutes of Health, Bethesda, Maryland 20892-1876, USA. FAU - Kehrl, J H AU - Kehrl JH LA - eng PT - Journal Article PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Antigens, CD) RN - 0 (Germinal Center Kinases) RN - 0 (NF-kappa B) RN - 0 (Proteins) RN - 0 (Receptors, Tumor Necrosis Factor) RN - 0 (Receptors, Tumor Necrosis Factor, Type I) RN - 0 (TNF Receptor-Associated Factor 1) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Amino Acid Sequence MH - Animals MH - Antigens, CD/*metabolism MH - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism MH - Cell Line MH - Enzyme Activation MH - Enzyme Induction MH - Germinal Center Kinases MH - Humans MH - JNK Mitogen-Activated Protein Kinases MH - *Mitogen-Activated Protein Kinases MH - Molecular Sequence Data MH - NF-kappa B/*metabolism MH - Protein Serine-Threonine Kinases/biosynthesis/chemistry/*metabolism MH - Proteins/*metabolism MH - Receptors, Tumor Necrosis Factor/*metabolism MH - Receptors, Tumor Necrosis Factor, Type I MH - Sequence Homology, Amino Acid MH - TNF Receptor-Associated Factor 1 EDAT- 1998/01/24 00:00 MHDA- 1998/01/24 00:01 CRDT- 1998/01/24 00:00 PHST- 1998/01/24 00:00 [pubmed] PHST- 1998/01/24 00:01 [medline] PHST- 1998/01/24 00:00 [entrez] AID - S0021-9258(18)39735-7 [pii] AID - 10.1074/jbc.272.51.32102 [doi] PST - ppublish SO - J Biol Chem. 1997 Dec 19;272(51):32102-7. doi: 10.1074/jbc.272.51.32102.