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PMID: 8551221 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

CD16-mediated p21ras activation is associated with Shc and p36 tyrosine phosphorylation and their binding with Grb2 in human natural killer cells.

The Journal of experimental medicine ·Vol. 183 ·No. 1 ·1996-01-01 ·Pages 179-86

Galandrini R, Palmieri G, Piccoli M, Frati L, Santoni A

Abstract

The Src homology (SH) 2/SH3 domain-containing protein Grb2 and the oncoprotein Shc have been implicated in a highly conserved mechanism that regulates p21ras activation. We investigated the involvement of these adaptor proteins in the signaling pathway induced by CD16 or interleukin (IL) 2R triggering in human natural killer (NK) cells. Both p46 and p52 forms of Shc were rapidly and transiently tyrosine phosphorylated upon CD16 or IL-2 stimulation with different kinetics. Shc immunoprecipitates from lysates of CD16- or IL-2-stimulated NK cells contained Grb2 and an unidentified 145-kD tyrosine phosphoprotein. Grb2 immunoprecipitates from anti-CD16-stimulated NK cells contained not only Shc, but also a 36-kD tyrosine phosphoprotein (p36). The interaction between Grb2 and Shc or p36 occurred via the Grb2SH2 domain as indicated by in vitro binding assays using a bacteriologically synthesized glutathione S-transferase-Grb2SH2 fusion protein. We also present evidence that p21ras is activated by CD16 and IL-2R cross-linking. Accumulation of guanosine triphosphate-bound Ras was detected within 1 minute and occurred with kinetics similar to inductive protein tyrosine phosphorylation and Grb2 association of Shc and p36 adaptor proteins.

MeSH Terms
Adaptor Proteins, Signal Transducing Adaptor Proteins, Vesicular Transport GRB2 Adaptor Protein Humans Immunoblotting Interleukin-2/pharmacology Killer Cells, Natural/drug effects,physiology Phosphoproteins/metabolism Phosphorylation Precipitin Tests Protein Binding Proteins/metabolism Proto-Oncogene Proteins p21(ras)/metabolism Receptors, IgG/metabolism Receptors, Interleukin-2/metabolism Recombinant Fusion Proteins/metabolism Shc Signaling Adaptor Proteins Signal Transduction/physiology Src Homology 2 Domain-Containing, Transforming Protein 1 Tyrosine/metabolism src Homology Domains
Chemicals
Adaptor Proteins, Signal Transducing Adaptor Proteins, Vesicular Transport GRB2 Adaptor Protein GRB2 protein, human Interleukin-2 Phosphoproteins Proteins Receptors, IgG Receptors, Interleukin-2 Recombinant Fusion Proteins SHC1 protein, human Shc Signaling Adaptor Proteins Src Homology 2 Domain-Containing, Transforming Protein 1 Tyrosine HRAS protein, human Proto-Oncogene Proteins p21(ras)
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Galandrini R
Department of Experimental Medicine and Pathology, University La Sapienza, Rome, Italy.
Palmieri G
Piccoli M
Frati L
Santoni A
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.183.1.179
Published
1996-01-01
Pages
179-86
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2192421
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.183.1.179 PMC Full Text View journal details
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