| Title: | Hematopoietic progenitor kinase 1 (HPK1) negatively regulates prostaglandin E2-induced fos gene transcription |
| Author(s): | Sawasdikosol S; Russo KM; Burakoff SJ; |
| Address: | "New York University Medical Center, Skirball Institute of Biomolecular Medicine, Department of Pathology, New York 10016, USA. sawasdik@saturn.med.nyu.edu" |
| DOI: | 10.1182/blood-2002-07-2316 |
| ISSN/ISBN: | 0006-4971 (Print) 0006-4971 (Linking) |
| Abstract: | "Prostaglandin E(2) (PGE(2)) is the predominant eicosanoid product released by macrophages at the site of inflammation. Binding of PGE(2) to its cognate 7 transmembrane-spanning G protein-coupled receptors (GPCRs) activates signaling pathways, leading to the synthesis of the Fos transcription factor. Because the Ste20 serine/threonine protein kinase (S/TPK) is a critical signal transducer for the G protein-coupled pheromone receptor in Saccharomyces cerevisiae, we postulated that the PGE(2) GPCRs may activate one of the Ste20 mammalian orthologs. We demonstrate here that the catalytic activity of a hematopoietic cell-restricted, Ste20-related S/TPK, HPK1, is positively regulated by exposure to physiological concentrations of PGE(2). Furthermore, ectopic expression studies implicated HPK1 as a negative regulator of PGE(2)-induced transcription of the fos gene. Our data suggest that PGE(2)-induced activation of HPK1 may represent a novel negative regulatory pathway capable of modulating PGE(2)-mediated gene transcription" |
| Keywords: | "Catalysis Cyclic AMP/pharmacology Dinoprostone/antagonists & inhibitors/*pharmacology Dose-Response Relationship, Drug Genes, Reporter *Genes, fos Humans Jurkat Cells/metabolism Neoplasm Proteins/drug effects/metabolism Promoter Regions, Genetic/drug effe;" |
| Notes: | "MedlineSawasdikosol, Sansana Russo, Kristin M Burakoff, Steven J eng CA70758/CA/NCI NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 2003/01/11 Blood. 2003 May 1; 101(9):3687-9. doi: 10.1182/blood-2002-07-2316. Epub 2003 Jan 9" |
