Mouse Ly-49A Interrupts Early Signaling Events in Natural Killer Cell Cytotoxicity and Functionally Associates with the SHP-1 Tyrosine Phosphatase

Nakamura, Mary C.; Niemi, Eréne C.; Fisher, Mark J.; Shultz, Leonard D.; Seaman, William E.; Ryan, James C.

doi:10.1084/jem.185.4.673

Article navigation

Article| February 17 1997

Mouse Ly-49A Interrupts Early Signaling Events in Natural Killer Cell Cytotoxicity and Functionally Associates with the SHP-1 Tyrosine Phosphatase

Mary C. Nakamura,

Mary C. Nakamura

From the *Department of Medicine, University of California, San Francisco, California 94143; the Veterans Administration Medical Center, San Francisco, California 94121; ‡The Jackson Laboratory, Bar Harbor, Maine 04609; and the §Department of Microbiology and Immunology, University of California, San Francisco, California 94143

Search for other works by this author on:

This Site

PubMed

Google Scholar

Eréne C. Niemi,

Eréne C. Niemi

From the *Department of Medicine, University of California, San Francisco, California 94143; the Veterans Administration Medical Center, San Francisco, California 94121; ‡The Jackson Laboratory, Bar Harbor, Maine 04609; and the §Department of Microbiology and Immunology, University of California, San Francisco, California 94143

Search for other works by this author on:

This Site

PubMed

Google Scholar

Mark J. Fisher,

Mark J. Fisher

From the *Department of Medicine, University of California, San Francisco, California 94143; the Veterans Administration Medical Center, San Francisco, California 94121; ‡The Jackson Laboratory, Bar Harbor, Maine 04609; and the §Department of Microbiology and Immunology, University of California, San Francisco, California 94143

Search for other works by this author on:

This Site

PubMed

Google Scholar

Leonard D. Shultz,

Leonard D. Shultz

From the *Department of Medicine, University of California, San Francisco, California 94143; the Veterans Administration Medical Center, San Francisco, California 94121; ‡The Jackson Laboratory, Bar Harbor, Maine 04609; and the §Department of Microbiology and Immunology, University of California, San Francisco, California 94143

Search for other works by this author on:

This Site

PubMed

Google Scholar

William E. Seaman,

William E. Seaman

From the *Department of Medicine, University of California, San Francisco, California 94143; the Veterans Administration Medical Center, San Francisco, California 94121; ‡The Jackson Laboratory, Bar Harbor, Maine 04609; and the §Department of Microbiology and Immunology, University of California, San Francisco, California 94143

Search for other works by this author on:

This Site

PubMed

Google Scholar

James C. Ryan

From the *Department of Medicine, University of California, San Francisco, California 94143; the Veterans Administration Medical Center, San Francisco, California 94121; ‡The Jackson Laboratory, Bar Harbor, Maine 04609; and the §Department of Microbiology and Immunology, University of California, San Francisco, California 94143

Search for other works by this author on:

This Site

PubMed

Google Scholar

Author and Article Information

Mary C. Nakamura , Eréne C. Niemi , Mark J. Fisher , Leonard D. Shultz , William E. Seaman , James C. Ryan

From the *Department of Medicine, University of California, San Francisco, California 94143; the Veterans Administration Medical Center, San Francisco, California 94121; ‡The Jackson Laboratory, Bar Harbor, Maine 04609; and the §Department of Microbiology and Immunology, University of California, San Francisco, California 94143

Address correspondence to Dr. Mary Nakamura, Immunology/Arthritis Section 111-R, Veterans Administration Medical Center, 4150 Clement Street, San Francisco, California 94121.

¹Abbreviations used in this paper: APT, phosphotyrosine; InsP₃, inositol triphosphates; ITIM, immunoreceptor tyrosine-based inhibitory motif; KIRs, killer inhibitory receptors; LAK, IL-2-activated NK cells.

Received: October 17 1996

Revision Received: December 26 1996

Online ISSN: 1540-9538

Print ISSN: 0022-1007

1997

J Exp Med (1997) 185 (4): 673–684.

https://doi.org/10.1084/jem.185.4.673

The lytic activity of natural killer (NK) cells is inhibited by the expression of class I major histocompatibility complex (MHC) antigens on target cells. In murine NK cells, Ly-49A mediates inhibition of cytotoxicity in response to the class I MHC antigen H-2D^d. In this report, we studied the function of mouse Ly-49A in both the rat NK cell tumor line, RNK-16, transfected with Ly-49A cDNA, and in primary NK cells. We show that ligation of Ly-49A by H-2D^d inhibits early signaling events during target cell stimulation, including polyphosphoinositide turnover and tyrosine phosphorylation. We also show that Ly-49A directly associates with the cytoplasmic tyrosine phosphatase SHP-1, and that Ly-49A function is impaired in NK cells from SHP-1 mutant viable motheaten mice and from SHP-1–deficient motheaten mice. Finally, we demonstrate that mutational substitution of the tyrosine within the proposed SHP-1 binding motif in Ly-49A completely abrogates inhibition of NK cell cytotoxicity through this receptor. These results demonstrate that Ly-49A interrupts early activating signals in NK cells, and that SHP-1 is an important mediator of Ly-49A function.

1997

You do not currently have access to this content.

Don't already have an account? Register

You could not be signed in. Please check your email address / username and password and try again.

Mouse Ly-49A Interrupts Early Signaling Events in Natural Killer Cell Cytotoxicity and Functionally Associates with the SHP-1 Tyrosine Phosphatase

Sign in

Client Account

Sign in via your Institution

Suggested Content

Email alerts

This Feature Is Available To Subscribers Only