PMID- 10449770
OWN - NLM
STAT- MEDLINE
DCOM- 19990909
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 17
DP  - 1999 Aug 17
TI  - SLAP, a dimeric adapter protein, plays a functional role in T cell receptor
      signaling.
PG  - 9775-80
AB  - Engagement of the T cell antigen receptor (TCR) leads to rapid activation of
      protein tyrosine kinases, which in turn phosphorylate downstream enzymes and
      adapter proteins. Some adapter proteins, such as SLP-76, Vav, and LAT, positively
      regulate TCR-mediated signal transduction, whereas others, such as Cbl, play an
      inhibitory role. SLAP (Src-like adapter protein), an adapter protein containing a
      Src homology 3 and a Src homology 2 domain, was isolated from a yeast interacting
      screen by using N-terminal Cbl as bait. N-terminal Cbl interacts with SLAP in
      vivo and in vitro in a tyrosine phosphorylation-independent manner. We observed
      that SLAP is expressed in T cells, and upon TCR activation, SLAP interacts with
      ZAP-70, Syk, LAT, and TCRzeta chain in Jurkat T cells. In transiently transfected
      COS-7 cells, SLAP forms separate complexes with ZAP-70, Syk, and LAT through its 
      Src homology 2 domain. Overexpression of a C-terminal-truncated SLAP mutant
      down-regulates nuclear factor of activated T cells-AP1 activity. We have evidence
      that SLAP forms homodimers through its C-terminal region. Serial truncations and 
      mutations in the C terminus of SLAP demonstrate that there is a correlation
      between the loss of dimerization and the inhibition of nuclear factor of
      activated T cells-AP1 activity. The in vivo association of SLAP with key
      signaling molecules and its inhibition of T cell activation suggests that SLAP
      plays an important role in TCR-mediated signal transduction.
FAU - Tang, J
AU  - Tang J
AD  - Department of Pediatric Oncology, Dana-Farber Cancer Institute and Department of 
      Pediatrics, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
FAU - Sawasdikosol, S
AU  - Sawasdikosol S
FAU - Chang, J H
AU  - Chang JH
FAU - Burakoff, S J
AU  - Burakoff SJ
LA  - eng
GR  - R01 CA070758/CA/NCI NIH HHS/United States
GR  - CA70758/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Enzyme Precursors)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (SLMAP protein, human)
RN  - 0 (SLP-76 signal Transducing adaptor proteins)
RN  - 0 (antigen T cell receptor, zeta chain)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (SYK protein, human)
RN  - EC 2.7.10.2 (Syk Kinase)
RN  - EC 2.7.10.2 (ZAP-70 Protein-Tyrosine Kinase)
RN  - EC 2.7.10.2 (ZAP70 protein, human)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Binding Sites
MH  - COS Cells
MH  - Dimerization
MH  - Enzyme Precursors/metabolism
MH  - Escherichia coli
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Jurkat Cells
MH  - Membrane Proteins/*physiology
MH  - Phosphoproteins/metabolism
MH  - Point Mutation
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Receptors, Antigen, T-Cell/*physiology
MH  - Saccharomyces cerevisiae
MH  - *Signal Transduction
MH  - Syk Kinase
MH  - ZAP-70 Protein-Tyrosine Kinase
PMC - PMC22286
EDAT- 1999/08/18 00:00
MHDA- 1999/08/18 00:01
CRDT- 1999/08/18 00:00
PHST- 1999/08/18 00:00 [pubmed]
PHST- 1999/08/18 00:01 [medline]
PHST- 1999/08/18 00:00 [entrez]
AID - 10.1073/pnas.96.17.9775 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9775-80. doi:
      10.1073/pnas.96.17.9775.