PMID- 11813163
OWN - NLM
STAT- MEDLINE
DCOM- 20020320
LR  - 20211203
IS  - 0014-2980 (Print)
IS  - 0014-2980 (Linking)
VI  - 32
IP  - 2
DP  - 2002 Feb
TI  - Vav cooperates with CD28 to induce NF-kappaB activation via a pathway involving 
      Rac-1 and mitogen-activated kinase kinase 1.
PG  - 447-56
AB  - CD28-delivered costimulatory signals are required to induce NF-kappaB activation 
      in response to TCR stimulation. We have recently demonstrated that the 
      mitogen-activated kinase kinase 1 (MEKK1), a kinase known to regulate the c-jun 
      N-terminal kinase (JNK) pathway, is also involved in the CD28- and TCR-induced 
      inhibitor of kappaB factor (IkappaB) kinases (IKK) and NF-kappaB activation. 
      Searching for molecules that couple TCR and CD28 to MEKK1, we found that the 
      guanine nucleotide exchange factor Vav synergized with CD28 stimulation in Jurkat 
      cells to induce NF-kappaB transcriptional activity through the activation of 
      IKKalpha and IKKbeta. Dominant negative mutants of Vav inhibited TCR- and 
      CD28-NF-kappaB-dependent transcription by interfering with the activation of the 
      IKK complex. Blocking Rac signaling downstream of Vav by dominant negative RacN17 
      exerts similar effects on IKK and NF-kappaB activation after TCR/CD28 
      stimulation. Finally, Vav-induced NF-kappaB activation in CD28 costimulated cells 
      was inhibited by dominant negative MEKK(KM). These results identify Vav, Rac-1 
      and MEKK1 as components of a common pathway regulating both NF-kappaB and AP-1 
      that contributes to full activation of the CD28 response element (CD28RE).
FAU - Marinari, Barbara
AU  - Marinari B
AD  - Department of Cellular and Developmental Biology, University of Rome La Sapienza, 
      Via del Sardi 70, I-00185 Rome, Italy.
FAU - Costanzo, Antonio
AU  - Costanzo A
FAU - Viola, Antonella
AU  - Viola A
FAU - Michel, Frederique
AU  - Michel F
FAU - Mangino, Giorgio
AU  - Mangino G
FAU - Acuto, Oreste
AU  - Acuto O
FAU - Levrero, Massimo
AU  - Levrero M
FAU - Piccolella, Enza
AU  - Piccolella E
FAU - Tuosto, Loretta
AU  - Tuosto L
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (CD28 Antigens)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-vav)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (VAV1 protein, human)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.10 (CHUK protein, human)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 2.7.11.10 (IKBKB protein, human)
RN  - EC 2.7.11.10 (IKBKE protein, human)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinase 1)
RN  - EC 2.7.11.25 (MAP3K1 protein, human)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
SB  - IM
MH  - CD28 Antigens/*metabolism
MH  - *Cell Cycle Proteins
MH  - Genes, Reporter
MH  - Humans
MH  - I-kappa B Kinase
MH  - Jurkat Cells
MH  - Luciferases/genetics
MH  - Lymphocyte Activation
MH  - *MAP Kinase Kinase Kinase 1
MH  - Mutation
MH  - NF-kappa B/*metabolism
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-vav
MH  - Receptors, Antigen, T-Cell/metabolism
MH  - Signal Transduction
MH  - T-Lymphocytes/immunology/metabolism
MH  - rac1 GTP-Binding Protein/genetics/*metabolism
EDAT- 2002/01/29 10:00
MHDA- 2002/03/21 10:01
CRDT- 2002/01/29 10:00
PHST- 2002/01/29 10:00 [pubmed]
PHST- 2002/03/21 10:01 [medline]
PHST- 2002/01/29 10:00 [entrez]
AID - 10.1002/1521-4141(200202)32:2<447::AID-IMMU447>3.0.CO;2-5 [doi]
PST - ppublish
SO  - Eur J Immunol. 2002 Feb;32(2):447-56. doi: 
      10.1002/1521-4141(200202)32:2<447::AID-IMMU447>3.0.CO;2-5.