PMID- 10477597
OWN - NLM
STAT- MEDLINE
DCOM- 19991004
LR  - 20211203
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 163
IP  - 6
DP  - 1999 Sep 15
TI  - TNF-mediated activation of the stress-activated protein kinase pathway: TNF 
      receptor-associated factor 2 recruits and activates germinal center kinase 
      related.
PG  - 3279-85
AB  - 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.
FAU - Shi, C S
AU  - Shi CS
AD  - B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National 
      Institute of Allergy and Infectious Disease, Bethesda, MD 20892, USA.
FAU - Leonardi, A
AU  - Leonardi A
FAU - Kyriakis, J
AU  - Kyriakis J
FAU - Siebenlist, U
AU  - Siebenlist U
FAU - Kehrl, J H
AU  - Kehrl JH
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Germinal Center Kinases)
RN  - 0 (NF-kappa B)
RN  - 0 (Proteins)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (Tumor Necrosis Factor-alpha)
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  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Catalytic Domain/immunology
MH  - Cell Line
MH  - Enzyme Activation/genetics/immunology
MH  - Germinal Center/*enzymology
MH  - Germinal Center Kinases
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Jurkat Cells
MH  - *Mitogen-Activated Protein Kinases
MH  - Molecular Sequence Data
MH  - NF-kappa B/metabolism
MH  - Protein Biosynthesis
MH  - Protein Serine-Threonine Kinases/biosynthesis/chemistry/*metabolism
MH  - Proteins/genetics/metabolism/*physiology
MH  - Receptors, Tumor Necrosis Factor/genetics/*physiology
MH  - Sequence Deletion
MH  - Signal Transduction/genetics/*immunology
MH  - TNF Receptor-Associated Factor 2
MH  - Tumor Necrosis Factor-alpha/genetics/*physiology
EDAT- 1999/09/08 00:00
MHDA- 1999/09/08 00:01
CRDT- 1999/09/08 00:00
PHST- 1999/09/08 00:00 [pubmed]
PHST- 1999/09/08 00:01 [medline]
PHST- 1999/09/08 00:00 [entrez]
AID - ji_v163n6p3279 [pii]
PST - ppublish
SO  - J Immunol. 1999 Sep 15;163(6):3279-85.