PMID- 11154209 OWN - NLM STAT- MEDLINE DCOM- 20010315 LR - 20220425 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 97 IP - 2 DP - 2001 Jan 15 TI - Signal transduction involved in MCP-1-mediated monocytic transendothelial migration. PG - 359-66 AB - Monocyte chemoattractant protein-1 (MCP-1) is a major chemoattractant for monocytes and T lymphocytes. The MonoMac6 cell line was used to examine MCP-1 receptor-mediated signal transduction events in relation to MCP-1-mediated monocytic transendothelial migration. MCP-1 stimulates, with distinct time courses, extracellular signal-related kinases (ERK1 and ERK2) and stress-activated protein kinases (SAPK1/JNK1 and SAPK2/p38). SAPK1/JNK1 activation was blocked by piceatannol, indicating that it is regulated by Syk kinase, whereas SAPK2/p38 activation was inhibited by PP2, revealing an upstream regulation by Src-like kinases. In contrast, ERK activation was insensitive to PP2 and piceatannol. Pertussis toxin, a blocker of Go/Gi proteins, abrogated MCP-1-induced ERK activation, but was without any effect on SAPK1/JNK1 and SAPK2/p38 activation. These results underscore the major implication of Go/Gi proteins and nonreceptor tyrosine kinases in the early MCP-1 signaling. Furthermore, MCP-1-mediated chemotaxis and transendothelial migration were significantly diminished by a high concentration of SB202190, a broad SAPK inhibitor, or by SB203580, a specific inhibitor of SAPK2/p38, and abolished by pertussis toxin treatment. Altogether, these data suggest that coordinated action of distinct signal pathways is required to produce a full response to MCP-1 in terms of monocytic locomotion. FAU - Cambien, B AU - Cambien B AD - INSERM U364, Faculte de Medecine, Nice, France. FAU - Pomeranz, M AU - Pomeranz M FAU - Millet, M A AU - Millet MA FAU - Rossi, B AU - Rossi B FAU - Schmid-Alliana, A AU - Schmid-Alliana A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Chemokine CCL2) RN - 0 (Enzyme Inhibitors) RN - 0 (Enzyme Precursors) RN - 0 (Fibronectins) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Virulence Factors, Bordetella) RN - 9012-63-9 (Cholera Toxin) RN - EC 2.4.2.31 (Pertussis Toxin) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.2 (SYK protein, human) RN - EC 2.7.10.2 (Syk Kinase) RN - EC 2.7.10.2 (src-Family Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 8) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases) SB - IM MH - Cell Line MH - Chemokine CCL2/*pharmacology MH - Chemotaxis/drug effects MH - Cholera Toxin/pharmacology MH - Endothelium, Vascular/cytology/physiology MH - Enzyme Activation/drug effects MH - Enzyme Inhibitors/pharmacology MH - Enzyme Precursors/drug effects/metabolism MH - Fibronectins/physiology MH - Humans MH - Intracellular Signaling Peptides and Proteins MH - Kinetics MH - Mitogen-Activated Protein Kinase 8 MH - Mitogen-Activated Protein Kinase Kinases/drug effects/metabolism MH - Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism MH - Monocytes/*cytology/drug effects MH - Pertussis Toxin MH - Protein-Tyrosine Kinases/drug effects/metabolism MH - Signal Transduction/*drug effects MH - Syk Kinase MH - Umbilical Cord/cytology MH - Virulence Factors, Bordetella/pharmacology MH - p38 Mitogen-Activated Protein Kinases MH - src-Family Kinases/drug effects/metabolism EDAT- 2001/01/12 11:00 MHDA- 2001/03/17 10:01 CRDT- 2001/01/12 11:00 PHST- 2001/01/12 11:00 [pubmed] PHST- 2001/03/17 10:01 [medline] PHST- 2001/01/12 11:00 [entrez] AID - S0006-4971(20)65997-3 [pii] AID - 10.1182/blood.v97.2.359 [doi] PST - ppublish SO - Blood. 2001 Jan 15;97(2):359-66. doi: 10.1182/blood.v97.2.359.