LCK-phosphorylated human killer cell-inhibitory receptors recruit and activate phosphatidylinositol 3-kinase Journal Article

   

Authors:	Marti, F.; Xu, C. W.; Selvakumar, A.; Brent, R.; Dupont, B.; King, P. D.
Article Title:	LCK-phosphorylated human killer cell-inhibitory receptors recruit and activate phosphatidylinositol 3-kinase
Abstract:	HLA-specific killer cell inhibitory receptors (KIR) are thought to impede natural killer (NK) and T cell activation programs through recruitment of the SH2 domain-containing tyrosine phosphatases, SHP-1 and SHP-2, to their cytoplasmic tails (CYT). To identify other SH2 domaincontaining proteins that bind KIR CYT, we used the recently described yeast two-bait interaction trap and a modified version of this system, both of which permit tyrosine phosphorylation of bait proteins. Using these systems, we show that KIR CYT, once phosphorylated by the src-family tyrosine kinase LCK, additionally bind the p85α regulatory subunit of phosphatidylinositol (PI) 3-kinase. Furthermore, we show that in an NK cell line, NK3.3, cross-linking of KIR results in recruitment of p85α to KIR and activation of PI 3-kinase lipid kinase activity. One consequence of KIR coupling to PI 3-kinase is downstream activation of the antiapoptotic protein kinase AKT. Therefore, in addition to providing negative signals, KIR may also contribute positive signals for NK and T cell growth and/or survival.
Keywords:	signal transduction; protein phosphorylation; unclassified drug; proto-oncogene proteins; nonhuman; protein conformation; protein domain; cell survival; cell growth; protein protein interaction; cell line; enzyme activation; protein tyrosine kinase; phosphorylation; phosphatidylinositol 3 kinase; saccharomyces cerevisiae; protein-serine-threonine kinases; intracellular signaling peptides and proteins; 1-phosphatidylinositol 3-kinase; proto-oncogene proteins c-akt; natural killer cell; killer cells, natural; protein tyrosine phosphatase; yeast; protein family; enzyme subunit; t lymphocyte activation; receptors, immunologic; hla system; protein kinase p60; protein-tyrosine-phosphatase; lymphocyte specific protein tyrosine kinase p56(lck); humans; priority journal; article; shp1 protein tyrosine phosphatase; src homology domains; killer cell inhibitory receptor
Journal Title:	Proceedings of the National Academy of Sciences of the United States of America
Volume:	95
Issue:	20
ISSN:	0027-8424
Publisher:	National Academy of Sciences
Date Published:	1998-09-29
Start Page:	11810
End Page:	11815
Language:	English
DOI:	10.1073/pnas.95.20.11810
PUBMED:	9751747
PROVIDER:	scopus
PMCID:	PMC21722
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0032578519&doi=10.1073%2fpnas.95.20.11810&partnerID=40&md5=a06635c6840972eaaa3e7a0e484403a9
Notes:	Article -- Export Date: 12 December 2016 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/102762