PYK2 Interacts with MyD88 and Regulates MyD88-mediated NF-kappaB Activation in Macrophages

Overview

Journal J Leukoc Biol

Publisher Oxford University Press

Specialty Allergy & Immunology

Date 2009 Dec 4

PMID 19955209

Citations 25

Authors

Cai-Xia Xi

Fei Xiong

Zheng Zhou

Lin Mei

Wen-Cheng Xiong

Affiliations

Soon will be listed here.

Abstract

PYK2, a major cell adhesion-activated tyrosine kinase, is highly expressed in macrophages and implicated in macrophage activation and inflammatory response. However, mechanisms by which PYK2 regulates inflammatory response are beginning to be understood. In this study, we demonstrate that PYK2 interacts with MyD88, a crucial signaling adaptor protein in LPS and PGN-induced NF-kappaB activation, in vitro and in macrophages. This interaction, increased in macrophages, stimulated by LPS, requires the death domain of MyD88. PYK2-deficient macrophages exhibit reduced phosphorylation and degradation of IkappaB, an inhibitor of NF-kappaB nuclear translocation, and decreased NF-kappaB activation and IL-1beta expression by LPS. These results suggest that via interaction with MyD88, PYK2 is involved in modulating cytokine (e.g., LPS) stimulation of NF-kappaB activity and signaling, providing a mechanism underlying PYK2 regulation of an inflammatory response.

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