TNF-mediated activation of the stress-activated protein kinase pathway: TNF receptor-associated factor 2 recruits and activates germinal center kinase related.
J Immunol
; 163(6): 3279-85, 1999 Sep 15.
Article
in En
| MEDLINE
| ID: mdl-10477597
TNF-induced activation of stress activated protein kinases (SAPKs, Jun NH2-terminal kinases) requires TNF receptor associated factor 2 (TRAF2). TRAF2 is a potent activator of a 95-kDa serine/threonine kinase termed germinal center kinase related (GCKR, also referred to as KHS1), which signals activation of the SAPK pathway. Consistent with a role for GCKR in TNF- induced SAPK activation, a kinase-inactive mutant of GCKR is a dominant negative inhibitor of TRAF2-induced SAPK activation. Here we show that TRAF2 interacts with GCKR. This interaction depended upon the TRAF domain of TRAF2 and the C-terminal 150 aa of GCKR. The full activation of GCKR by TRAF2 required the TRAF2 RING finger domain. TNF treatment of a T cell line, Jurkat, increased both GCRK and SAPK activity and enhanced the coimmunoprecipitation of GCKR with TRAF2. Similar results were found with the B cell line HS-Sultan. These findings are consistent with a model whereby TNF signaling results in the recruitment and activation of GCKR by TRAF2, which leads to SAPK activation.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Proteins
/
Tumor Necrosis Factor-alpha
/
Protein Serine-Threonine Kinases
/
Receptors, Tumor Necrosis Factor
/
Calcium-Calmodulin-Dependent Protein Kinases
/
Germinal Center
/
Mitogen-Activated Protein Kinases
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
J Immunol
Year:
1999
Document type:
Article
Affiliation country:
United States
Country of publication:
United States