PMID- 12618212 OWN - NLM STAT- MEDLINE DCOM- 20040105 LR - 20190922 IS - 0898-6568 (Print) IS - 0898-6568 (Linking) VI - 15 IP - 4 DP - 2003 Apr TI - Formylpeptides trigger selective molecular pathways that are required in the physiological functions of human neutrophils. PG - 377-83 AB - For-Met-Delta(z)Leu-Phe-OMe ([Delta(z)Leu(2)]) is a conformationally restricted for-Met-Leu-Phe-OMe (fMLP-OMe) analogue able to discriminate between different responses of human neutrophils. In contrast, [Delta(z)Leu(2)] significantly activates the transduction pathways-involving Ca(2+), inositol phosphate, and cyclic AMP (cAMP) enhancement, as is the case with the full agonist fMLP-OMe. Here, we have studied the specific involvement of protein kinase C (PKC) isoforms and mitogen activated protein kinases (MAPKs) in the presence or absence of extracellular Ca(2+), being the cation clearly involved in the activation of neutrophils by fMLP. A strong correlation has been found between PKC isoforms, MAPKs and the selective physiological functions by [Delta(z)Leu(2)]-activated neutrophils. In a calcium-free condition, our data suggest that the failure of PKC beta1 translocation and of p38 MAPK phosphorylation by the analogue refers to its inability to induce chemotaxis, and that the failure by both fMLP-OMe and [Delta(z)Leu(2)] to evoke extracellular response kinase 1 and 2 (ERK1/2) phosphorylation would suggest a reduction in superoxide anion production. FAU - Selvatici, Rita AU - Selvatici R AD - Dipartimento di Medicina Sperimentale e Diagnostica, Sezione Genetica Medica, Via L Borsari 46, Universita degli Studi di Ferrara, 44100 Ferrara, Italy. FAU - Falzarano, Sofia AU - Falzarano S FAU - Traniello, Serena AU - Traniello S FAU - Pagani Zecchini, Giampiero AU - Pagani Zecchini G FAU - Spisani, Susanna AU - Spisani S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Cell Signal JT - Cellular signalling JID - 8904683 RN - 11062-77-4 (Superoxides) RN - 137320-56-0 (formyl-methionyl-delta(Z)-dehydroleucyl-phenylalanine methyl ester) RN - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine) RN - 65929-03-5 (formylmethionyl-leucyl-phenylalanine methyl ester) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases) RN - SY7Q814VUP (Calcium) SB - IM MH - Calcium/pharmacology MH - Calcium Signaling/*drug effects MH - Cells, Cultured MH - *Chemotaxis, Leukocyte/drug effects MH - Enzyme Activation MH - Humans MH - In Vitro Techniques MH - Mitogen-Activated Protein Kinase Kinases/metabolism MH - N-Formylmethionine Leucyl-Phenylalanine/*analogs & derivatives/*pharmacology MH - Neutrophils/*drug effects/enzymology/physiology MH - Phosphorylation MH - Protein Kinase C/metabolism MH - Superoxides EDAT- 2003/03/06 04:00 MHDA- 2004/01/06 05:00 CRDT- 2003/03/06 04:00 PHST- 2003/03/06 04:00 [pubmed] PHST- 2004/01/06 05:00 [medline] PHST- 2003/03/06 04:00 [entrez] AID - S0898656802001237 [pii] AID - 10.1016/s0898-6568(02)00123-7 [doi] PST - ppublish SO - Cell Signal. 2003 Apr;15(4):377-83. doi: 10.1016/s0898-6568(02)00123-7.