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Interleukin-1 Receptor-Associated Kinase-1 (IRAK-1) functionally associates with PKCepsilon and VASP in the regulation of macrophage migration.

Abstract：

:Macrophage migration is mediated by complex cellular signaling processes and cytoskeleton re-arrangement. In particular, recent advances indicate that the innate immunity signaling process plays a key role in the regulation of macrophage migration. In this report, we have provided evidence demonstrating the involvement of a key innate immunity signaling kinase, Interleukin-1 Receptor-Associated Kinase-1 (IRAK-1) as a critical modulator of macrophage migration. Macrophage migration induced by phorbol 12-myristate 13-acetate (PMA) is significantly attenuated in IRAK-1(-/-) macrophages as compared to wild type macrophages. Mechanistically, we demonstrated that IRAK-1 works downstream of PKCepsilon and upstream of VASP, a member of Ena/VASP family proteins. IRAK-1 forms a close complex with PKCepsilon as well as VASP, and participates in PMA-induced phosphorylation of VASP. Notably, IRAK-1 contains a novel EVH1 domain binding motif (L(167)WPPPP) within its N-terminus, which is responsible for its interaction with VASP. The mutant IRAK-1 (L167A/W168A) fails to associate with VASP. Our findings provide a novel facet regarding the molecular signaling process regulating macrophage migration.

journal_name

Mol Immunol

journal_title

Molecular immunology

authors

Gan L,Li L

doi

10.1016/j.molimm.2009.12.004

subject

Has Abstract

pub_date

2010-03-01 00:00:00

pages

1278-82

issue

6

eissn

0161-5890

issn

1872-9142

pii

S0161-5890(09)00860-8

journal_volume

47

pub_type

杂志文章

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