PMID- 10395673
OWN - NLM
STAT- MEDLINE
DCOM- 19990729
LR  - 20181201
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 163
IP  - 2
DP  - 1999 Jul 15
TI  - Tyrosine phosphorylation of Vav stimulates IL-6 production in mast cells by a
      Rac/c-Jun N-terminal kinase-dependent pathway.
PG  - 802-10
AB  - This study investigates whether the guanine nucleotide exchange activity of Vav
      is linked to cytokine production in mast cells. Overexpression of Vav in the
      RBL-2H3 mast cell line resulted in the constitutive tyrosine phosphorylation and 
      activation of Vav. We analyzed the functional effect of Vav overexpression on
      cytokine production. IL-2 and IL-6 mRNA levels were dramatically increased in
      Vav-overexpressing cells and correlated with increased NF-AT activity. Little or 
      no effect was observed on the mRNA levels of IL-3, IL-4, GM-CSF, TNF-alpha, and
      TGF-beta. FcepsilonRI engagement did not further enhance IL-2 and IL-6 mRNA
      levels and only slightly enhanced NF-AT activity, but dramatically increased the 
      mRNA levels of other tested cytokines. To understand the signal transduction
      required, we focused primarily on IL-6 induction by measuring mitogen-activated
      protein kinase activity and analyzing the effects of mutant or dominant negative 
      forms of Vav, Rac1, and c-Jun N-terminal kinase-1 (JNK1). Vav overexpression
      resulted in the constitutive activation of JNK1 with little or no effect on p38
      mitogen-activated protein kinase and ERK2. This was dependent on Vav-mediated
      activation of Rac1 as a Dbl domain-mutated Vav, inactive Rac N17, and inactive
      JNK1 down-regulated the Vav-induced JNK1 or IL-6 responses. Vav expression, but
      not expression of domain-mutated Vav, increased IL-6 secretion from
      nonimmortalized bone marrow-derived mast cells upon FcepsilonRI engagement. We
      conclude that Vav phosphorylation contributes to IL-6 induction in mast cells.
FAU - Song, J S
AU  - Song JS
AD  - Section on Chemical Immunology, National Institute of Arthritis and
      Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA.
FAU - Haleem-Smith, H
AU  - Haleem-Smith H
FAU - Arudchandran, R
AU  - Arudchandran R
FAU - Gomez, J
AU  - Gomez J
FAU - Scott, P M
AU  - Scott PM
FAU - Mill, J F
AU  - Mill JF
FAU - Tan, T H
AU  - Tan TH
FAU - Rivera, J
AU  - Rivera J
LA  - eng
SI  - GENBANK/U39476
PT  - Journal Article
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA, Complementary)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Interleukin-2)
RN  - 0 (Interleukin-6)
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-vav)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, IgE)
RN  - 0 (Transcription Factors)
RN  - 0 (Vav1 protein, rat)
RN  - 42HK56048U (Tyrosine)
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 Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - EC 3.6.5.2 (rac GTP-Binding Proteins)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - AIM
SB  - IM
MH  - Adjuvants, Immunologic/physiology
MH  - Animals
MH  - Bone Marrow Cells/immunology/metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinases/antagonists &
      inhibitors/biosynthesis/genetics/metabolism/*physiology
MH  - *Cell Cycle Proteins
MH  - Cell Line
MH  - DNA, Complementary/biosynthesis
MH  - DNA-Binding Proteins/biosynthesis/genetics/metabolism
MH  - Enzyme Activation/immunology
MH  - GTP-Binding Proteins/*physiology
MH  - Interleukin-2/biosynthesis/genetics
MH  - Interleukin-6/*biosynthesis/genetics/metabolism
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Mast Cells/enzymology/*metabolism
MH  - Mitogen-Activated Protein Kinase 1
MH  - *Mitogen-Activated Protein Kinases
MH  - NFATC Transcription Factors
MH  - *Nuclear Proteins
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins/biosynthesis/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-vav
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Receptors, IgE/physiology
MH  - Signal Transduction/*immunology
MH  - Transcription Factors/biosynthesis/genetics/metabolism
MH  - Transfection
MH  - Tyrosine/*metabolism
MH  - p38 Mitogen-Activated Protein Kinases
MH  - rac GTP-Binding Proteins
MH  - ras Proteins/physiology
EDAT- 1999/07/08 00:00
MHDA- 1999/07/08 00:01
CRDT- 1999/07/08 00:00
PHST- 1999/07/08 00:00 [pubmed]
PHST- 1999/07/08 00:01 [medline]
PHST- 1999/07/08 00:00 [entrez]
AID - ji_v163n2p802 [pii]
PST - ppublish
SO  - J Immunol. 1999 Jul 15;163(2):802-10.