Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Signal transduction involved in MCP-1-mediated monocytic transendothelial migration. 1115 9

Fractalkine displays features that distinguishes it from the other chemokines. In particular, besides its chemoattractant action it promotes, under physiologic flow, the rapid capture and the firm adhesion of a subset of leukocytes or intervenes in the neuron/microglia interaction. This study verified that indeed the human monocytic MonoMac6 cell line adheres to fibronectin-coated filters in response to soluble fractalkine (s-FKN). s-FKN stimulates, with distinct time courses, extracellular signal-related kinases (ERK1 and ERK2) and stress-activated protein kinases (SAPK1/JNK1 and SAPK2/p38). Both p60 Src and p72 Syk were activated under s-FKN stimulation with a rapid kinetic profile compatible with a downstream regulation on the mitogen-activated protein kinase (MAPK) congeners. The use of specific tyrosine kinase inhibitors revealed that the ERK pathway is strictly controlled by Syk, whereas c-Src up-regulated the downstream SAPK2/p38. In contrast, the SAPK1/JNK1 pathway was not regulated by any of these nonreceptor tyrosine kinases. The s-FKN-mediated increased adherence of MonoMac6 cells was partially inhibited by SB202190, a broad SAPKs inhibitor, PD98059, an MEK inhibitor, LY294002, a phosphatidyl inositol 3-kinase inhibitor, and a pertussis toxin-sensitive G protein. These data highlight that the integration of a complex array of signal transduction pathways is necessary to complete the full s-FNK-dependent adherence of human monocytic cells to fibronectin. (Blood. 2001;97:2031-2037)
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PMID:Signal transduction pathways involved in soluble fractalkine-induced monocytic cell adhesion. 1126 68