Rac2 Specificity in Macrophage Integrin Signaling: Potential role for Syk kinase

De Pradip, Xiaodong Peng, Donald L. Durden

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Herein we report that, despite the similarity of Rac2 to Racl (92% amino acid identity), macrophages derived from Rac2-/- mice, which continue to express Rac1, display a marked defect in αvβ 3vβ5 and α 4β1 integrin-directed migration measured on vitronectin and fibronectin fragments (FN-H296), respectively. In contrast, mouse embryo fibroblasts derived from the Rac2 knockout mice utilize Rac1 for migration via αvβ3vβ 5 and α4β1. The genetic reconstitution of bone marrow-derived macrophages (BMMθ) with Rac2 restores the integrin-dependent migration of Rac2-deficient macrophages on vitronectin (VN) and FN-H296. The levels of GTP-Rac2 generated upon specific integrin engagement in wild type macrophages parallels the phenotypic defect observed in Rac2-deficient macrophages; i.e. FN-H296, α 4β1 > VN, αvβ 3vβ5 > FN-CH271, α 5β1 > intact FN. In a COS7 cell system, the expression of Syk kinase alone is sufficient to convert the α 4β1 migration response to Rac2 dependence. Therefore, we present the first evidence that the α4β1 receptor in blood cells has evolved a Syk-Rac2 signaling axis to transmit signals required for integrin-directed migration suggesting that Syk kinase in part encodes myeloid Rac2 specificity in vivo.

Original languageEnglish (US)
Pages (from-to)41661-41669
Number of pages9
JournalJournal of Biological Chemistry
Volume278
Issue number43
DOIs
StatePublished - Oct 24 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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