ROCK1 functions as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability

Sasidhar Vemula, Jianjian Shi, Philip Hanneman, Lei Wei, Reuben Kapur

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Rho kinases belong to a family of serine/threonine kinases whose role in recruitment and migration of inflammatory cells is poorly understood. We show that deficiency of ROCK1 results in increased recruitment and migration of macrophages and neutrophils in vitro and in vivo. Enhanced migration resulting from ROCK1 deficiency is observed despite normal expression of ROCK2 and a significant reduction in overall ROCK activity. ROCK1 directly binds PTEN in response to receptor activation and is essential for PTEN phosphorylation and stability. In the absence of ROCK1, PTEN phosphorylation, stability, and its activity are significantly impaired. Consequently, increased activation of downstream targets of PTEN, including PIP3, AKT, GSK-3β, and cyclin D1, is observed. Our results reveal ROCK1 as a physiologic regulator of PTEN whose function is to repress excessive recruitment of macrophages and neutrophils during acute inflammation.

Original languageEnglish
Pages (from-to)1785-1796
Number of pages12
JournalBlood
Volume115
Issue number9
DOIs
StatePublished - Mar 4 2010

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Phosphorylation
Macrophages
Cell Movement
Chemical activation
Glycogen Synthase Kinase 3
rho-Associated Kinases
Neutrophil Infiltration
Protein-Serine-Threonine Kinases
Cyclin D1
Neutrophils
Cells
Inflammation
In Vitro Techniques

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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ROCK1 functions as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability. / Vemula, Sasidhar; Shi, Jianjian; Hanneman, Philip; Wei, Lei; Kapur, Reuben.

In: Blood, Vol. 115, No. 9, 04.03.2010, p. 1785-1796.

Research output: Contribution to journalArticle

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