Chemoattractant receptor-stimulated F-actin polymerization in the human neutrophil is signaled by 2 distinct pathways.
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 2 distinct signaling pathways of actin polymerization in the pseudopod region: a phosphoinositide 3-kinase gamma (PI3Kgamma)-dependent and -independent pathway. The PI3Kgamma dependent signaling of F-actin polymerization also depends on protein kinase C zeta and protein kinase B (Akt/PKB). The PI3Kgamma-independent pathway depends on GTPase RhoA, the RhoA ROCK kinase, Src family tyrosine kinases, and NADPH, and is modulated by cAMP.
Chodniewicz
David
D
Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC 27708-0300, USA.
Zhelev
Doncho V
DV
D000199:Actins / Q000378:metabolism*; D058544:Class Ib Phosphatidylinositol 3-Kinase; D000242:Cyclic AMP / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D018715:Microscopy, Video; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000502:physiology*; D018000:Receptors, Peptide / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D000199:Actins; D058544:Class Ib Phosphatidylinositol 3-Kinase; D000242:Cyclic AMP; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D019061:src-Family Kinases; C546760:PIK3CG protein, human