{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T08:13:01Z","timestamp":1697703181814},"reference-count":54,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2009,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Parathyroid hormone (PTH) activates multiple signaling pathways following binding to the PTH1 receptor in osteoblasts. Previous work revealed a discrepancy between cAMP stimulation and CRE reporter activation of truncated PTH peptides, suggesting that additional signaling pathways contribute to activation of the CRE. Using a CRE\u2010Luciferase reporter containing multiple copies of the CRE stably transfected into the osteoblastic cell line Saos\u20102, we tested the ability of modulators of alternative pathways to activate the CRE or block the PTH\u2010induced activation of the CRE. Activators of non\u2010cyclic AMP pathways, that is, EGF (Akt, MAPK, JAK\/STAT pathways); thapsigargin (intracellular calcium pathway); phorbol myristate acetate (protein kinase C, PKC pathway) induced minor increases in CRE\u2010luciferase activity alone but induced dramatic synergistic effects in combination with PTH. The protein kinase A (PKA) inhibitor H\u201089 (10 \u00b5M) almost completely blocked PTH\u2010induced activation of the CRE\u2010reporter. Adenylate cyclase inhibitors SQ 22536 and DDA had profound and time\u2010dependent biphasic effects on the CRE response. The MAPK inhibitor PD 98059 partially inhibited basal and PTH\u2010induced CRE activity to the same degree, while the PKC inhibitor bisindolylmaleimide (BIS) had variable effects. The calmodulin kinase II inhibitor KN\u201093 had no significant effect on the response to PTH. We conclude that non\u2010cAMP pathways (EGF pathway, calcium pathway, PKC pathway) converge on, and have synergistic effects on, the response of a CRE reporter to PTH. J. Cell. Biochem. 106: 887\u2013895, 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.22057","type":"journal-article","created":{"date-parts":[[2009,1,30]],"date-time":"2009-01-30T19:26:41Z","timestamp":1233343601000},"page":"887-895","source":"Crossref","is-referenced-by-count":2,"title":["Parathyroid hormone synergizes with non\u2010cyclic AMP pathways to activate the cyclic AMP response element"],"prefix":"10.1002","volume":"106","author":[{"given":"Richard J.","family":"Murrills","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer L.","family":"Andrews","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachelle L.","family":"Samuel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerie 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