PMID- 7945333 OWN - NLM STAT- MEDLINE DCOM- 19941031 LR - 20211203 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 203 IP - 3 DP - 1994 Sep 30 TI - Role of serine/threonine protein kinases in the induction of JE, a platelet-derived growth factor inducible gene. PG - 1815-20 AB - Platelet-derived growth factor (PDGF) and serum both stimulate the transcription of the mouse early response gene, JE. JE and its human homolog, macrophage chemotactic protein-1 (MCP-1), encode potent monocyte chemotactic factors. JE/MCP-1 is a member of the chemokine superfamily of small inducible genes whose products are multifaceted mediators of inflammatory and immune responses. We now report evidence that the serine/threonine kinase inhibitors H7 and H8 but not HA1004, W-7, and ML-7 inhibit the transcriptional induction of the JE gene by serum whereas the phosphatase inhibitor, okadaic acid, increases JE expression. Downregulation of protein kinase C by prior exposure to TPA does not inhibit the induction of JE by serum, nor does it affect the inhibition of JE induction by H7. These results suggest that one or more serine/threonine kinases may be important in the signal transduction mechanism that leads to the induction of the JE gene. FAU - Kawahara, R S AU - Kawahara RS AD - Department of Medicine, Jewish Hospital at Washington University Medical Center, St. Louis, MO 63110. FAU - Deng, Z W AU - Deng ZW FAU - Denkinger, D J AU - Denkinger DJ FAU - Deuel, T F AU - Deuel TF LA - eng GR - CA49712/CA/NCI NIH HHS/United States GR - HL14147/HL/NHLBI NIH HHS/United States GR - HL31102/HL/NHLBI NIH HHS/United States GR - etc. PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Chemokine CCL2) RN - 0 (Chemotactic Factors) RN - 0 (Culture Media) RN - 0 (Cytokines) RN - 0 (Ethers, Cyclic) RN - 0 (Isoquinolines) RN - 0 (Piperazines) RN - 0 (Platelet-Derived Growth Factor) RN - 0 (Protein Kinase Inhibitors) RN - 0 (RNA, Messenger) RN - 1W21G5Q4N2 (Okadaic Acid) RN - 84477-87-2 (1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine) RN - 84478-11-5 (N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) SB - IM GS - JE GS - MCP-1 MH - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine MH - 3T3 Cells MH - Animals MH - Cell Nucleus/metabolism MH - Chemokine CCL2 MH - Chemotactic Factors/*biosynthesis MH - Culture Media MH - Cytokines/*biosynthesis MH - Ethers, Cyclic/pharmacology MH - Gene Expression/*drug effects MH - Humans MH - Isoquinolines/pharmacology MH - Mice MH - Mice, Inbred BALB C MH - Okadaic Acid MH - Piperazines/pharmacology MH - Platelet-Derived Growth Factor/*pharmacology MH - Protein Kinase Inhibitors MH - Protein Serine-Threonine Kinases/*metabolism MH - RNA, Messenger/biosynthesis MH - Transcription, Genetic/drug effects EDAT- 1994/09/30 00:00 MHDA- 1994/09/30 00:01 CRDT- 1994/09/30 00:00 PHST- 1994/09/30 00:00 [pubmed] PHST- 1994/09/30 00:01 [medline] PHST- 1994/09/30 00:00 [entrez] AID - S0006-291X(84)72398-9 [pii] AID - 10.1006/bbrc.1994.2398 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 1994 Sep 30;203(3):1815-20. doi: 10.1006/bbrc.1994.2398.