title: Inhibition of chemotactic peptide-induced development of cell polarity and locomotion by the protein kinase C inhibitor CGP 41 251 in human neutrophils correlates with inhibition of protein phosphorylation.
abstract: Several protein kinase inhibitors of the staurosporine type displaying different enzyme specificity were used to study the role of protein kinase C (PKC) in motile neutrophil functions. Effects on protein phosphorylation, F-actin localization, morphology, and locomotion were determined. Only staurosporine, but not another inhibitor more specific for PKC (CGP 41 251) or inhibitors of cyclic nucleotide-dependent kinases (KT 5720, KT 5822), induced formation of F-actin-enriched surface protrusions at nanomolar concentrations in initially spherical neutrophils. The inhibitor with the highest specificity for PKC, CGP 41 251, had no effect on morphology and F-actin localization of resting cells up to 1 microM. However, this inhibitor suppressed front-tail polarity and locomotion in chemotactic peptide-stimulated cells. The cells became nonpolar with surface projections instead. Inhibition of front-tail polarity induced by CGP 41 251 strongly correlated with inhibition of in situ phosphorylation of a 67-kDa protein (IC50 = 0.2 microM), whereas induction of polarity by chemotactic peptide was associated with increased phosphorylation of this protein. Kinase inhibitors inactive on PKC (KT 5720, KT 5822) did not affect development of front-tail polarity. We conclude that a kinase involved in the phosphorylation of a 67-kDa protein, very likely a PKC isoform, may be important for the development of cell polarity and locomotion. In contrast, chemotactic peptide-induced formation of actin-containing protrusions may not be mediated by this enzyme.
authors.affiliation: Department of Pathology, University of Bern, Switzerland.
authors.forename: V
authors.initials: V
authors.lastname: Niggli
authors.forename: H
authors.initials: H
authors.lastname: Keller
mesh_terms: D000199:Actins / Q000187:drug effects; D000470:Alkaloids / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D016764:Cell Polarity / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008970:Molecular Weight; D009504:Neutrophils / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011506:Proteins / Q000378:metabolism; D019311:Staurosporine / Q000031:analogs & derivatives
chemical_list: D000199:Actins; D000470:Alkaloids; D011506:Proteins; D011493:Protein Kinase C; D019311:Staurosporine; C059539:midostaurin