Publication Date:
1996-05-24
Description:
The absence of CTLA-4 results in uncontrolled T cell proliferation. The T cell receptor-specific kinases FYN, LCK, and ZAP-70 as well as the RAS pathway were found to be activated in T cells of Ctla-4-/- mutant mice. In addition, CTLA-4 specifically associated with the tyrosine phosphatase SYP, an interaction mediated by the SRC homology 2 (SH2) domains of SYP and the phosphotyrosine sequence Tyr-Val-Lys-Met within the CTLA-4 cytoplasmic tail. The CTLA-4-associated SYP had phosphatase activity toward the RAS regulator p52SHC. Thus, the RAS pathway and T cell activation through the T cell receptor are regulated by CTLA-4-associated SYP.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marengere, L E -- Waterhouse, P -- Duncan, G S -- Mittrucker, H W -- Feng, G S -- Mak, T W -- New York, N.Y. -- Science. 1996 May 24;272(5265):1170-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉AMGEN Institute, Toronto, Ontario, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8638161" target="_blank"〉PubMed〈/a〉
Keywords:
Abatacept
;
*Adaptor Proteins, Signal Transducing
;
*Adaptor Proteins, Vesicular Transport
;
Amino Acid Sequence
;
Animals
;
Antigens, CD
;
Antigens, CD3/metabolism
;
Antigens, Differentiation/chemistry/*metabolism
;
CTLA-4 Antigen
;
GRB2 Adaptor Protein
;
*Immunoconjugates
;
Intracellular Signaling Peptides and Proteins
;
Lymphocyte Activation
;
Mice
;
Mice, Inbred C57BL
;
Molecular Sequence Data
;
Mutation
;
Phosphorylation
;
Protein Tyrosine Phosphatase, Non-Receptor Type 11
;
Protein Tyrosine Phosphatase, Non-Receptor Type 6
;
Protein Tyrosine Phosphatases/*metabolism
;
Protein-Tyrosine Kinases/metabolism
;
Proteins/metabolism
;
Receptors, Antigen, B-Cell/metabolism
;
Receptors, Antigen, T-Cell/*metabolism
;
Recombinant Fusion Proteins/metabolism
;
SH2 Domain-Containing Protein Tyrosine Phosphatases
;
Shc Signaling Adaptor Proteins
;
*Signal Transduction
;
T-Lymphocytes/immunology/*metabolism
;
ras Proteins/metabolism
;
src Homology Domains
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
