期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 293, 期 1, 页码 463-469出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/S0006-291X(02)00238-3
关键词
p70S6K ribosomal kinase; chemotaxis; cell signaling; GM-CSF; neutrophils
资金
- NHLBI NIH HHS [HL056653, R29 HL056653, R01 HL056653-08, R01 HL056653] Funding Source: Medline
We report here for the first time that the specific MAPK kinase (MEK) inhibitor, PD-98059, completely knocked out granulocyte-macrophage colony-stimulating factor (GM-CSF)-stimulated MAPK activity but also partially inactivated the ribosomal kinase p70S6K. Since a connection between the two major signaling pathways, Ras/MEK/MAPK and P13-K/p7OS6K was suspected, experiments were designed to prove a molecular crosstalk between those. First, p70S6K protein could be co-immunoprecipitated with anti-MAPK antibodies, MAPK protein was similarly present in anti-p70S6K immunoprecipitates, indicating close spatial proximity of both signaling molecules. Second, p70S6K enzymatic activity was found in anti-MAPK immunoprecipitates and MAPK in anti-p70S6K immunoprecipitates, being the latter activity higher in samples derived from GM-CSF-treated cells. Since an upstream activator of p70S6K, phosphatidylinositol (PI)3-kinase, has been associated to cell movement in phagocytic cells, we studied a possible participation of p70S6K in chemotaxis and whether MAPK had an input. Our data show that functional chemotaxis was inhibited by rapamycin, a specific p70S6K inhibitor, as well as by PD-98059. Thus, a connection between these two kinases extends from the molecular level to cell migration, a key functionality in non-proliferative, mature phagocytes such as neutrophils. (C) 2002 Elsevier Science (USA). All rights reserved.
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