Expression of RAC2 in endothelial cells is required for the postnatal neovascular response

Pradip De, Qiong Peng, Dmitry O. Traktuevc, Weiming Li, Mervin C. Yoder, Keith L. March, Donald L. Durden

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Herein, we describe an obligate role for the hematopoietic specific GTPase, RAC2 in endothelial integrin signaling and the postnatal neovascularization response in vivo. Using a Rac2 knockout mouse model, we discovered that despite the presence of both RAC1 and RAC2 protein in endothelial cells, RAC2 is obligately required for the postnatal neovascular response and αvβ3/α4β1/α5β1 integrin-directed migration on vitronectin, H296 and CH271, fibronectin fragments, respectively. The molecular basis for RAC2 specificity was explored. A genetic analysis of Syk -/+ or Syk-/+;Rac2 -/+ mice revealed that SYK kinase is required for the integrin induced activation of RAC2. The analysis of endothelial cells from Rac2-/+ versus Syk-/+;Rac2-/+ mice provided genetic evidence that SYK-RAC2 signaling axis regulates integrin (αvβ3, α4β1 and α5β1) dependent migration. Our results provide evidence that a specific region of the nonreceptor protein tyrosine kinase, SYK, the B linker region containing Y342 and Y346 is required for SYK's regulation of RAC2 and integrin dependent migration. Moreover, the capacity of mice to vascularize the ischemic hindlimb following femoral artery ligation or matrigel plugs was markedly reduced in mice homozygous deficient for the Rac2 gene. These findings identify a novel signaling axis for the induction and potential modulation of postnatal angiogenesis.

Original languageEnglish (US)
Pages (from-to)248-263
Number of pages16
JournalExperimental Cell Research
Volume315
Issue number2
DOIs
StatePublished - Jan 15 2009

Fingerprint

Integrins
Endothelial Cells
Vitronectin
GTP Phosphohydrolases
Femoral Artery
Hindlimb
Fibronectins
Knockout Mice
Protein-Tyrosine Kinases
Ligation
Phosphotransferases
Genes
Proteins

Keywords

  • Angiogenesis
  • Endothelial cells
  • Integrin
  • RAC2
  • SYK

ASJC Scopus subject areas

  • Cell Biology

Cite this

De, P., Peng, Q., Traktuevc, D. O., Li, W., Yoder, M. C., March, K. L., & Durden, D. L. (2009). Expression of RAC2 in endothelial cells is required for the postnatal neovascular response. Experimental Cell Research, 315(2), 248-263. https://doi.org/10.1016/j.yexcr.2008.10.003

Expression of RAC2 in endothelial cells is required for the postnatal neovascular response. / De, Pradip; Peng, Qiong; Traktuevc, Dmitry O.; Li, Weiming; Yoder, Mervin C.; March, Keith L.; Durden, Donald L.

In: Experimental Cell Research, Vol. 315, No. 2, 15.01.2009, p. 248-263.

Research output: Contribution to journalArticle

De, P, Peng, Q, Traktuevc, DO, Li, W, Yoder, MC, March, KL & Durden, DL 2009, 'Expression of RAC2 in endothelial cells is required for the postnatal neovascular response', Experimental Cell Research, vol. 315, no. 2, pp. 248-263. https://doi.org/10.1016/j.yexcr.2008.10.003
De, Pradip ; Peng, Qiong ; Traktuevc, Dmitry O. ; Li, Weiming ; Yoder, Mervin C. ; March, Keith L. ; Durden, Donald L. / Expression of RAC2 in endothelial cells is required for the postnatal neovascular response. In: Experimental Cell Research. 2009 ; Vol. 315, No. 2. pp. 248-263.
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