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Prepublished online as a Blood First Edition Paper on January 9, 2003; DOI 10.1182/blood-2002-07-2316.
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Blood, 1 May 2003, Vol. 101, No. 9, pp. 3687-3689
BRIEF REPORT: PHAGOCYTES
Hematopoietic progenitor kinase 1 (HPK1) negatively
regulates prostaglandin E2-induced fos gene
transcription
Sansana Sawasdikosol,
Kristin M. Russo, and
Steven J. Burakoff
From the New York University Medical Center, Skirball
Institute of Biomolecular Medicine, Department of Pathology, New
York.
Prostaglandin E2 (PGE2) is the
predominant eicosanoid product released by macrophages at the site of
inflammation. Binding of PGE2 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 PGE2 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 PGE2. Furthermore, ectopic expression
studies implicated HPK1 as a negative regulator of
PGE2-induced transcription of the fos gene. Our
data suggest that PGE2-induced activation of HPK1 may represent a novel negative regulatory pathway capable of modulating PGE2-mediated gene transcription.

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