PMID- 18759929
OWN - NLM
STAT- MEDLINE
DCOM- 20081103
LR  - 20091119
IS  - 1600-065X (Electronic)
IS  - 0105-2896 (Linking)
VI  - 224
DP  - 2008 Aug
TI  - Control of lymphocyte development and activation by negative regulatory 
      transmembrane adapter proteins.
PG  - 215-28
LID - 10.1111/j.1600-065X.2008.00656.x [doi]
AB  - Signals emanating from antigen receptors critically regulate immune cell 
      activation, survival, and differentiation. Transmembrane adapter proteins 
      (TRAPs), a group of molecules that organize signaling complexes at the plasma 
      membrane, play a pivotal role in propagating and fine-tuning antigen 
      receptor-mediated signaling. During the last years, it has been demonstrated that 
      most of the TRAPs possess inhibitory functions, including linker for activation 
      of T cells (LAT), the best characterized adapter that links the T-cell receptor 
      (TCR) to Ca(2+) flux and mitogen-activated protein kinase activation. Indeed, it 
      appears that LAT may assemble inhibitory complexes that trigger negative feedback 
      loops, thus terminating T-cell activation. Additionally, recent data demonstrate 
      that SIT [Src homology 2 domain-containing phosphatase 2 (SHP2)-interacting TRAP] 
      fine-tunes TCR-mediated signaling events and negatively regulates T-cell 
      development and homeostasis. The experimental evidence suggests that TRAPs play a 
      crucial role also in establishing tolerance. In fact, loss of SIT, LAX, or NTAL 
      (non-T cell activation linker)/linker for activation of B cells (LAB) resulted in 
      the spontaneous development of autoimmune diseases. Moreover, we recently showed 
      that in addition to the inhibition of Src-family kinases, PAG (phosphoprotein 
      associated with glycosphingolipid-enriched domains) is also involved in the 
      negative regulation of Ras activation. Collectively, these data demonstrate that 
      TRAPs are important modulators of immune cell activation and function. Finally, 
      it appears that TRAPs possess redundant yet not completely overlapping functions.
FAU - Simeoni, Luca
AU  - Simeoni L
AD  - Institute of Molecular and Clinical Immunology, Otto-von-Guericke University, 
      Magdeburg, Germany.
FAU - Lindquist, Jonathan A
AU  - Lindquist JA
FAU - Smida, Michal
AU  - Smida M
FAU - Witte, Vanessa
AU  - Witte V
FAU - Arndt, Boerge
AU  - Arndt B
FAU - Schraven, Burkhart
AU  - Schraven B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Immunol Rev
JT  - Immunological reviews
JID - 7702118
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (Antigens, Differentiation, T-Lymphocyte)
RN  - 0 (LAT protein, human)
RN  - 0 (Membrane Proteins)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/immunology/*metabolism
MH  - Adaptor Proteins, Vesicular Transport/immunology/metabolism
MH  - Animals
MH  - Antigens, Differentiation, T-Lymphocyte/*immunology
MH  - Autoimmune Diseases/immunology
MH  - Cell Differentiation/immunology
MH  - Feedback, Physiological/*immunology
MH  - Humans
MH  - Immune System/cytology/growth & development/*immunology/metabolism
MH  - Lymphocyte Activation/immunology
MH  - Lymphocytes/cytology/immunology/*metabolism
MH  - Membrane Proteins/immunology/*metabolism
MH  - Signal Transduction/*immunology
MH  - src Homology Domains
RF  - 118
EDAT- 2008/09/02 09:00
MHDA- 2008/11/04 09:00
CRDT- 2008/09/02 09:00
PHST- 2008/09/02 09:00 [pubmed]
PHST- 2008/11/04 09:00 [medline]
PHST- 2008/09/02 09:00 [entrez]
AID - IMR656 [pii]
AID - 10.1111/j.1600-065X.2008.00656.x [doi]
PST - ppublish
SO  - Immunol Rev. 2008 Aug;224:215-28. doi: 10.1111/j.1600-065X.2008.00656.x.