PMID- 9103241 OWN - NLM STAT- MEDLINE DCOM- 19970502 LR - 20220227 IS - 0741-5400 (Print) IS - 0741-5400 (Linking) VI - 61 IP - 4 DP - 1997 Apr TI - MCP-1-mediated chemotaxis requires activation of non-overlapping signal transduction pathways. PG - 529-32 AB - Monocyte chemoattractant protein-1 (MCP-1) is a CC chemokine that attracts monocytes and T lymphocytes. Its receptor (CCR2) is a heptahelical G-protein-coupled receptor (GPCR) whose signal transduction pathways for chemotaxis have not been completely defined. Because other GPCRs stimulate the mitogen-activated protein kinase (MAPK) cascade, we examined this pathway's activity in response to MCP-1. MCP-1 induced rapid and transient activation of MAPK in human monocytes and in Chinese hamster ovary cells expressing CCR2B. This effect was largely insensitive to pertussis toxin and wortmannin, and was protein kinase C-dependent and protein tyrosine kinase-independent. PD 098059, an inhibitor of MEK activation, not only prevented MAPK activation but also inhibited MCP-1-induced chemotaxis. Because pertussis toxin and wortmannin also efficiently inhibit chemotaxis but do not completely inhibit MAPK activation, these data may define non-overlapping signal transduction pathways that all must be activated to produce chemokine-mediated chemotaxis. FAU - Yen, H AU - Yen H AD - Division of Neoplastic Disease Mechanisms, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. FAU - Zhang, Y AU - Zhang Y FAU - Penfold, S AU - Penfold S FAU - Rollins, B J AU - Rollins BJ LA - eng GR - CA53091/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (CCR2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Receptors, CCR2) RN - 0 (Receptors, Chemokine) RN - 0 (Receptors, Cytokine) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) SB - IM MH - Animals MH - CHO Cells/cytology/enzymology MH - Calcium-Calmodulin-Dependent Protein Kinases/metabolism MH - Chemokine CCL2/*physiology MH - Chemotaxis, Leukocyte/*physiology MH - Cricetinae MH - Enzyme Activation MH - Humans MH - Kinetics MH - Leukocytes, Mononuclear/cytology/enzymology MH - Mitogen-Activated Protein Kinase 1 MH - Protein-Tyrosine Kinases/metabolism MH - Receptors, CCR2 MH - *Receptors, Chemokine MH - Receptors, Cytokine/metabolism MH - Signal Transduction/*physiology EDAT- 1997/04/01 00:00 MHDA- 1997/04/01 00:01 CRDT- 1997/04/01 00:00 PHST- 1997/04/01 00:00 [pubmed] PHST- 1997/04/01 00:01 [medline] PHST- 1997/04/01 00:00 [entrez] AID - 10.1002/jlb.61.4.529 [doi] PST - ppublish SO - J Leukoc Biol. 1997 Apr;61(4):529-32. doi: 10.1002/jlb.61.4.529.