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Prepublished online as a Blood First Edition Paper on October 3, 2002; DOI 10.1182/blood-2002-05-1435.
Submitted May 17, 2002
Accepted September 4, 2002
Chemoattractant receptor-stimulated F-actin polymerization in the human neutrophil is signaled by two distinct pathways
David Chodniewicz* and Doncho V Zhelev
Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, USA
* Corresponding author; email: d.chod{at}duke.edu.
We characterized the overall rate of F-actin polymerization in the pseudopod region by measuring the rate of extension of single pseudopods stimulated by f-Met-Leu-Phe. The rate of pseudopod extension was measured in the presence of inhibitors for signaling molecules that are known to be involved in motility. Our data show the existence of two distinct signaling pathways of actin polymerization in the pseudopod region: a phosphoinositide 3-kinase  (PI3K) dependent and -independent pathway. The PI3K dependent signaling of F-actin polymerization also depends on protein kinase C  and protein kinase B (Akt/PKB). The PI3K independent pathway depends on GTPase RhoA, the RhoA ROCK kinase, Src family tyrosine kinases and NADPH, and is modulated by cAMP.
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