Phospholipase Cγ negatively regulates Rac/Cdc42 activation in antigen-stimulated mast cells

Mirvat El-Sibai, Jonathan M. Backer

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The Rho GTPases Rac and Cdc42 play a central role in the regulation of secretory and cytoskeletal responses in antigen-stimulated mast cells. In this study, we examine the kinetics and mechanism of Rac and Cdc42 activation in the rat basophilic leukemia RBL-21-13 cells. The activation kinetics of both Rac and Cdc42 show a biphasic profile, consisting of an early transient peak at 1 min and a late sustained activation phase at 20-40 min. The inhibition of phospholipase C (PLC)γ causes a twofold increase in Rac and Cdc42 activation that coincides with a dramatic production of atypical filopodia-like structures. Inhibition of protein kinase C using bisindolylmaleimide mimics the effect of PLCγ inhibition on Rac activation, but not on Cdc42 activation. In contrast, depletion of intracellular calcium leads to a complete inhibition of the early activation peak of both Rac and Cdc42, without significant effects on the late sustained activation. These data suggest that PLCγ is involved in a negative feedback loop that leads to the inhibition of Rac and Cdc42. They also suggest that the presence of intracellular calcium is a prerequisite for both Rac and Cdc42 activation.

Original languageEnglish (US)
Pages (from-to)261-270
Number of pages10
JournalEuropean Journal of Immunology
Volume37
Issue number1
DOIs
StatePublished - Jan 2007

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Type C Phospholipases
Mast Cells
Antigens
Calcium
rho GTP-Binding Proteins
Pseudopodia
Protein Kinase C
Leukemia

Keywords

  • Calcium
  • Cdc42
  • Masy cells
  • Phospholipase C
  • Rac

ASJC Scopus subject areas

  • Immunology

Cite this

Phospholipase Cγ negatively regulates Rac/Cdc42 activation in antigen-stimulated mast cells. / El-Sibai, Mirvat; Backer, Jonathan M.

In: European Journal of Immunology, Vol. 37, No. 1, 01.2007, p. 261-270.

Research output: Contribution to journalArticle

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