The small GTPase Rap1 is highly expressed in human neutrophils,
but its function is largely unknown. Using the Rap1-
binding domain of RalGDS (RalGDS-RBD) as an activationspecific
probe for Rap1, we have investigated the regulation
of Rap1 activity in primary human neutrophils. We found
that a variety of stimuli involved in neutrophil activation,
including fMet-Leu-Phe (fMLP), platelet-activating factor
(PAF), granulocyte-macrophage colony-stimulating factor
(GM-CSF), and IgG-coated particles, induce a rapid and
transient Rap1 activation. In addition, we found that Rap1 is
normally activated in neutrophils from chronic granulomatous
disease patients that lack cytochrome b558 or p47phox
and have a defective NADPH oxidase system. From these
results we conclude that in neutrophils Rap1 is activated
independently of respiratory burst induction. Finally, we
found that Rap1 is activated by both the Ca21 ionophore
ionomycin and the phorbol ester 12-O-tetradecanoylphorbol
13-acetate (TPA), indicating that phospholipase C (PLC)
activation leading to elevated levels of intracellular free Ca21
and diacylglycerol (DAG) can mediate Rap1 activation. However,
inhibition of PLC and Ca21 depletion only marginally
affected fMLP-induced Rap1 activation, suggesting that additional
pathways may control Rap1 activation
Is data on this page outdated, violates copyrights or anything else? Report the problem now and we will take corresponding actions after reviewing your request.