PMID- 18835194
OWN - NLM
STAT- MEDLINE
DCOM- 20081215
LR  - 20231213
IS  - 1097-4180 (Electronic)
IS  - 1074-7613 (Print)
IS  - 1074-7613 (Linking)
VI  - 29
IP  - 4
DP  - 2008 Oct 17
TI  - Inhibitory receptor signaling via tyrosine phosphorylation of the adaptor Crk.
PG  - 578-88
LID - 10.1016/j.immuni.2008.07.014 [doi]
AB  - Many cellular responses, such as autoimmunity and cytotoxicity, are controlled by 
      receptors with cytoplasmic immunoreceptor tyrosine-based inhibition motifs 
      (ITIMs). Here, we showed that binding of inhibitory natural killer (NK) cell 
      receptors to human leukocyte antigen (HLA) class I on target cells induced 
      tyrosine phosphorylation of the adaptor Crk, concomitant with dephosphorylation 
      of the guanine exchange factor Vav1. Furthermore, Crk dissociated from the 
      guanine exchange factor C3G and bound to the tyrosine kinase c-Abl during 
      inhibition. Membrane targeting of a tyrosine-mutated form of Crk could overcome 
      inhibition of NK cell cytotoxicity, providing functional evidence that Crk 
      phosphorylation contributes to inhibition. The specific phosphorylation of Crk 
      and its dissociation from a signaling complex, observed here with two types of 
      inhibitory receptors, expands the signaling potential of the large ITIM-receptor 
      family and reveals an unsuspected component of the inhibitory mechanism.
FAU - Peterson, Mary E
AU  - Peterson ME
AD  - Laboratory of Immunogenetics, National Institute of Allergy and Infectious 
      Diseases, National Institutes of Health, Rockville, MD 20852, USA.
FAU - Long, Eric O
AU  - Long EO
LA  - eng
GR  - Z01 AI000525-20/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20081002
PL  - United States
TA  - Immunity
JT  - Immunity
JID - 9432918
RN  - 0 (BCAR1 protein, human)
RN  - 0 (Crk-Associated Substrate Protein)
RN  - 0 (Guanine Nucleotide-Releasing Factor 2)
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (NK Cell Lectin-Like Receptor Subfamily D)
RN  - 0 (Proto-Oncogene Proteins c-crk)
RN  - 0 (Proto-Oncogene Proteins c-vav)
RN  - 0 (Receptors, KIR)
RN  - 0 (Receptors, Natural Killer Cell)
RN  - 0 (VAV1 protein, human)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-cbl)
RN  - EC 2.7.10.2 (Proto-Oncogene Proteins c-abl)
RN  - EC 3.1.3.48 (PTPN6 protein, human)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 6)
SB  - IM
CIN - Immunity. 2008 Oct 17;29(4):515-7. PMID: 18957262
MH  - Amino Acid Motifs/immunology
MH  - Animals
MH  - Crk-Associated Substrate Protein/immunology/metabolism
MH  - Guanine Nucleotide-Releasing Factor 2/immunology/metabolism
MH  - HLA Antigens/immunology/metabolism
MH  - Histocompatibility Antigens Class I/immunology/metabolism
MH  - Humans
MH  - Killer Cells, Natural/*immunology/metabolism
MH  - NK Cell Lectin-Like Receptor Subfamily D/immunology/metabolism
MH  - Phosphorylation
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 6/immunology/metabolism
MH  - Proto-Oncogene Proteins c-abl/immunology/metabolism
MH  - Proto-Oncogene Proteins c-cbl/immunology/metabolism
MH  - Proto-Oncogene Proteins c-crk/immunology/*metabolism
MH  - Proto-Oncogene Proteins c-vav/immunology/metabolism
MH  - Rats
MH  - Receptors, KIR/immunology/*metabolism
MH  - Receptors, Natural Killer Cell/immunology/metabolism
MH  - HLA-E Antigens
PMC - PMC2639764
MID - NIHMS74844
EDAT- 2008/10/07 09:00
MHDA- 2008/12/17 09:00
PMCR- 2009/10/01
CRDT- 2008/10/07 09:00
PHST- 2008/02/18 00:00 [received]
PHST- 2008/06/25 00:00 [revised]
PHST- 2008/07/30 00:00 [accepted]
PHST- 2008/10/07 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/10/07 09:00 [entrez]
PHST- 2009/10/01 00:00 [pmc-release]
AID - S1074-7613(08)00407-X [pii]
AID - 10.1016/j.immuni.2008.07.014 [doi]
PST - ppublish
SO  - Immunity. 2008 Oct 17;29(4):578-88. doi: 10.1016/j.immuni.2008.07.014. Epub 2008 
      Oct 2.