PMID- 10021361
OWN - NLM
STAT- MEDLINE
DCOM- 19990323
LR  - 20190728
IS  - 0960-9822 (Print)
IS  - 0960-9822 (Linking)
VI  - 9
IP  - 2
DP  - 1999 Jan 28
TI  - The hematopoietic-specific adaptor protein gads functions in T-cell signaling via
      interactions with the SLP-76 and LAT adaptors.
PG  - 67-75
AB  - BACKGROUND: The adaptor protein Gads is a Grb2-related protein originally
      identified on the basis of its interaction with the tyrosine-phosphorylated form 
      of the docking protein Shc. Gads protein expression is restricted to
      hematopoietic tissues and cell lines. Gads contains a Src homology 2 (SH2)
      domain, which has previously been shown to have a similar binding specificity to 
      that of Grb2. Gads also possesses two SH3 domains, but these have a distinct
      binding specificity to those of Grb2, as Gads does not bind to known Grb2 SH3
      domain targets. Here, we investigated whether Gads is involved in T-cell
      signaling. RESULTS: We found that Gads is highly expressed in T cells and that
      the SLP-76 adaptor protein is a major Gads-associated protein in vivo. The
      constitutive interaction between Gads and SLP-76 was mediated by the
      carboxy-terminal SH3 domain of Gads and a 20 amino-acid proline-rich region in
      SLP-76. Gads also coimmunoprecipitated the tyrosine-phosphorylated form of the
      linker for activated T cells (LAT) adaptor protein following cross-linking of the
      T-cell receptor; this interaction was mediated by the Gads SH2 domain.
      Overexpression of Gads and SLP-76 resulted in a synergistic augmentation of
      T-cell signaling, as measured by activation of nuclear factor of activated T
      cells (NFAT), and this cooperation required a functional Gads SH2 domain.
      CONCLUSIONS: These results demonstrate that Gads plays an important role in
      T-cell signaling via its association with SLP-76 and LAT. Gads may promote
      cross-talk between the LAT and SLP-76 signaling complexes, thereby coupling
      membrane-proximal events to downstream signaling pathways.
FAU - Liu, S K
AU  - Liu SK
AD  - Department of Medical Biophysics, University of Toronto, The Arthur and Sonia
      Labatt Brain Tumour Research Centre, Hospital for Sick Children, Research
      Institute, 555 University Ave, Toronto, Ontario M5G 1X8, Canada.
FAU - Fang, N
AU  - Fang N
FAU - Koretzky, G A
AU  - Koretzky GA
FAU - McGlade, C J
AU  - McGlade CJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Curr Biol
JT  - Current biology : CB
JID - 9107782
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (GRAP2 protein, human)
RN  - 0 (LAT protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (SLP-76 signal Transducing adaptor proteins)
RN  - 0 (Transcription Factors)
RN  - 42HK56048U (Tyrosine)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - Carrier Proteins/*metabolism/*physiology
MH  - DNA-Binding Proteins/metabolism
MH  - Humans
MH  - Jurkat Cells
MH  - *Membrane Proteins
MH  - NFATC Transcription Factors
MH  - *Nuclear Proteins
MH  - Phosphoproteins/chemistry/*metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Receptors, Antigen, T-Cell/metabolism
MH  - *Signal Transduction
MH  - T-Lymphocytes/*metabolism
MH  - Transcription Factors/metabolism
MH  - Tyrosine/metabolism
EDAT- 1999/02/18 00:00
MHDA- 1999/02/18 00:01
CRDT- 1999/02/18 00:00
PHST- 1999/02/18 00:00 [pubmed]
PHST- 1999/02/18 00:01 [medline]
PHST- 1999/02/18 00:00 [entrez]
AID - S0960-9822(99)80017-7 [pii]
AID - 10.1016/s0960-9822(99)80017-7 [doi]
PST - ppublish
SO  - Curr Biol. 1999 Jan 28;9(2):67-75. doi: 10.1016/s0960-9822(99)80017-7.