PMID- 10488157
OWN - NLM
STAT- MEDLINE
DCOM- 19991104
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 39
DP  - 1999 Sep 24
TI  - Requirement of the Src homology 2 domain protein Shb for T cell
      receptor-dependent activation of the interleukin-2 gene nuclear factor for
      activation of T cells element in Jurkat T cells.
PG  - 28050-7
AB  - Stimulation of the T cell antigen receptor (TCR) induces tyrosine phosphorylation
      of numerous intracellular proteins. We have recently investigated the role of the
      adaptor protein Shb in the early events of T cell signaling and observed that Shb
      associates with Grb2, linker for activation of T cells (LAT) and the TCR
      zeta-chain in Jurkat cells. We now report that Shb also associates with
      phospholipase C-gamma1 (PLC-gamma1) in these cells. Overexpression of Src
      homology 2 domain defective Shb caused diminished phosphorylation of LAT and
      consequently the activation of mitogen-activated protein kinases was decreased
      upon TCR stimulation. In addition, the Shb mutant also blocked phosphorylation of
      PLC-gamma1 and the increase in cytoplasmic Ca(2+) following TCR stimulation.
      Nuclear factor for activation of T cells is a major target for Ras and calcium
      signaling pathways in T cells following TCR stimulation, and the overexpression
      of the mutant Shb prevented TCR-dependent activation of the nuclear factor for
      activation of T cells. Consequently, endogenous interleukin-2 production was
      decreased under these conditions. The results indicate a role for Shb as a link
      between the TCR and downstream signaling events involving LAT and PLC-gamma1 and 
      resulting in the activation of transcription of the interleukin-2 gene.
FAU - Lindholm, C K
AU  - Lindholm CK
AD  - Department of Medical Cell Biology, Box 571, Biomedicum, Uppsala University,
      S-75123 Uppsala, Sweden.
FAU - Gylfe, E
AU  - Gylfe E
FAU - Zhang, W
AU  - Zhang W
FAU - Samelson, L E
AU  - Samelson LE
FAU - Welsh, M
AU  - Welsh M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (GRB2 Adaptor Protein)
RN  - 0 (GRB2 protein, human)
RN  - 0 (Interleukin-2)
RN  - 0 (Isoenzymes)
RN  - 0 (Membrane Proteins)
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Recombinant Proteins)
RN  - 0 (SHB protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (antigen T cell receptor, zeta chain)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.1.4.- (Type C Phospholipases)
RN  - EC 3.1.4.3 (Phospholipase C gamma)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - Amino Acid Substitution
MH  - Calcium/metabolism
MH  - Cytoplasm/metabolism
MH  - DNA-Binding Proteins/*metabolism
MH  - ErbB Receptors/immunology
MH  - GRB2 Adaptor Protein
MH  - Gene Expression Regulation/immunology
MH  - Humans
MH  - Interleukin-2/*genetics
MH  - Isoenzymes/metabolism
MH  - Jurkat Cells
MH  - Lymphocyte Activation
MH  - Membrane Proteins/*immunology
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - NFATC Transcription Factors
MH  - *Nuclear Proteins
MH  - Phospholipase C gamma
MH  - Phosphorylation
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Proteins/immunology
MH  - Proto-Oncogene Proteins/genetics/*metabolism
MH  - Receptors, Antigen, T-Cell/*immunology
MH  - Recombinant Proteins/metabolism
MH  - T-Lymphocytes/*immunology
MH  - Transcription Factors/*metabolism
MH  - Transfection
MH  - Type C Phospholipases/metabolism
MH  - src Homology Domains
EDAT- 1999/09/17 00:00
MHDA- 1999/09/17 00:01
CRDT- 1999/09/17 00:00
PHST- 1999/09/17 00:00 [pubmed]
PHST- 1999/09/17 00:01 [medline]
PHST- 1999/09/17 00:00 [entrez]
AID - 10.1074/jbc.274.39.28050 [doi]
AID - S0021-9258(19)52220-7 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Sep 24;274(39):28050-7. doi: 10.1074/jbc.274.39.28050.