Cytokine Signaling and Hematopoietic Homeostasis Are Disrupted in Lnk-deficient Mice

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2002 Jun 19

PMID 12070287

Citations 111

Authors

Laura Velazquez

Alec M Cheng

Heather E Fleming

Caren Furlonger

Shirly Vesely

Alan Bernstein

Christopher J Paige

Tony Pawson

Affiliations

Soon will be listed here.

Abstract

The adaptor protein Lnk, and the closely related proteins APS and SH2B, form a subfamily of SH2 domain-containing proteins implicated in growth factor, cytokine, and immunoreceptor signaling. To elucidate the physiological function of Lnk, we derived Lnk-deficient mice. Lnk(-/-) mice are viable, but display marked changes in the hematopoietic compartment, including splenomegaly and abnormal lymphoid and myeloid homeostasis. The in vitro proliferative capacity and absolute numbers of hematopoietic progenitors from Lnk(-/-) mice are greatly increased, in part due to hypersensitivity to several cytokines. Moreover, an increased synergy between stem cell factor and either interleukin (IL)-3 or IL-7 was observed in Lnk(-/-) cells. Furthermore, Lnk inactivation causes abnormal modulation of IL-3 and stem cell factor-mediated signaling pathways. Consistent with these results, we also show that Lnk is highly expressed in multipotent cells and committed precursors in the erythroid, megakaryocyte, and myeloid lineages. These data implicate Lnk as playing an important role in hematopoiesis and in the regulation of growth factor and cytokine receptor-mediated signaling.

Citing Articles

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