{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T10:04:19Z","timestamp":1770717859677,"version":"3.49.0"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[1997,11,3]],"date-time":"1997-11-03T00:00:00Z","timestamp":878515200000},"content-version":"vor","delay-in-days":175,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["FEBS Letters"],"published-print":{"date-parts":[[1997,5,12]]},"abstract":"<jats:p>Rat C6 glioma cells have been used to characterize molecular events involved in the regulation of inducible nitric oxide synthase (iNOS) gene expression stimulated by interferon\u2010\u03b3 (IFN\u2010\u03b3) plus lipopolysaccharide (LPS). IFNs induce a signaling event which involves activation of Stat1 transcription factor. Previous studies have shown that IFNs also induce extracellular signal\u2010regulated kinase\/mitogen\u2010activated protein kinase (ERK\/MAPK) activation. However, the mechanisms by which IFNs stimulate MAPK activation remain elusive. Here we show that in C6 glioma cells, transiently expressing the dominant\u2010negative form of c\u2010Ha\u2010Ras (Asn\u201017) abrogated IFN\u2010\u03b3\u2010induced ERK1 and ERK2 activation. Furthermore, PD98059, a specific MEK1 inhibitor, also blocked this activation. These results indicate that p21<jats:sup>\n<jats:italic>ras<\/jats:italic>\n<\/jats:sup> and MEK1 are required for IFN\u2010\u03b3\u2010induced ERK1 and ERK2 activation. Recent studies have reported that MAPK is responsible for serine phosphorylation of Stat1 which is required for Stat1's DNA binding and maximal transcriptional activity. Thus, we examined the role of the Ras\u2010MAPK pathway in Stat1 activation and subsequent iNOS induction in C6 glioma cells. Further experiments showed that neither Asn\u201017 Ras expression nor concentrations of PD98059, which completely abrogated IFN\u2010\u03b3\u2010induced ERK1 and ERK2 activation, affected Stat1 DNA binding activity or iNOS induction, indicating that the Ras\u2010MAPK pathway does not appear to be involved in the activation of Stat1 and subsequent iNOS induction in C6 glioma cells.<\/jats:p>","DOI":"10.1016\/s0014-5793(97)00383-9","type":"journal-article","created":{"date-parts":[[2002,7,25]],"date-time":"2002-07-25T16:08:36Z","timestamp":1027613316000},"page":"33-38","source":"Crossref","is-referenced-by-count":46,"title":["Activation of Stat1 and subsequent transcription of inducible nitric oxide synthase gene in C6 glioma cells is independent of interferon\u2010\u03b3\u2010induced MAPK activation that is mediated by p21<sup><i>ras<\/i><\/sup>"],"prefix":"10.1002","volume":"408","author":[{"given":"Tadashi","family":"Nishiya","sequence":"first","affiliation":[]},{"given":"Takashi","family":"Uehara","sequence":"additional","affiliation":[]},{"given":"Hiroki","family":"Edamatsu","sequence":"additional","affiliation":[]},{"given":"Yoshito","family":"Kaziro","sequence":"additional","affiliation":[]},{"given":"Hiroshi","family":"Itoh","sequence":"additional","affiliation":[]},{"given":"Yasuyuki","family":"Nomura","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[1997,11,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90266-6"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.6.12.1381691"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.178.2.749"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(93)80954-S"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.177.6.1779"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.20.9730"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1994.62020811.x"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(95)00933-Z"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(96)00417-9"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81277-5"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90311-9"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7569900"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.153.5.2146"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.2.1111"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.8.8.3235"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(91)01013-R"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/17.15.6419"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.9.4314"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(87)90021-2"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1993.tb18215.x"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.17.7686"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7701321"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)98601-1"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)54548-8"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(91)01033-X"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.52.30837"},{"key":"e_1_2_6_28_1","doi-asserted-by":"crossref","unstructured":"Wang X.Y. Fuhrer D.K. Marshall M.S. and Yang Y.-C. (1995) J. Biol. Chem. 270 47 27999\u201328002.","DOI":"10.1074\/jbc.270.47.27999"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)37599-3"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.8.3974"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb07192.x"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.27.16449"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.50.31863"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00541.x"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(95)00076-L"}],"container-title":["FEBS Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1016%2FS0014-5793%2897%2900383-9","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1016%2FS0014-5793(97)00383-9","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/S0014-5793%2897%2900383-9","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,16]],"date-time":"2023-09-16T03:18:23Z","timestamp":1694834303000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1016\/S0014-5793%2897%2900383-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,5,12]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1997,5,12]]}},"alternative-id":["10.1016\/S0014-5793(97)00383-9"],"URL":"https:\/\/doi.org\/10.1016\/s0014-5793(97)00383-9","archive":["Portico"],"relation":{},"ISSN":["0014-5793","1873-3468"],"issn-type":[{"value":"0014-5793","type":"print"},{"value":"1873-3468","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,5,12]]}}}