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dc.contributor.authorJenkins, BJ
dc.contributor.authorGrail, D
dc.contributor.authorInglese, M
dc.contributor.authorQuilici, C
dc.contributor.authorBozinovski, S
dc.contributor.authorWong, P
dc.contributor.authorErnst, M
dc.date.available2014-05-21T19:22:21Z
dc.date.issued2004-02-01
dc.identifierhttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000188744000002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=d4d813f4571fa7d6246bdc0dfeca3a1c
dc.identifier.citationJenkins, B. J., Grail, D., Inglese, M., Quilici, C., Bozinovski, S., Wong, P. & Ernst, M. (2004). Imbalanced gp130-dependent signaling in macrophages alters macrophage colony-stimulating factor responsiveness via regulation of c-fms expression. MOLECULAR AND CELLULAR BIOLOGY, 24 (4), pp.1453-1463. https://doi.org/10.1128/MCB.24.4.1453-1463.2004.
dc.identifier.issn0270-7306
dc.identifier.urihttp://hdl.handle.net/11343/26183
dc.descriptionC1 - Journal Articles Refereed
dc.description.abstractThe mechanisms by which interleukin-6 (IL-6) family cytokines, which utilize the common receptor signaling subunit gp130, influence monocyte/macrophage development remain unclear. Here we have utilized macrophages devoid of either gp130-dependent STAT1/3 (gp130(Delta STAT/Delta STAT)) or extracellular signal-regulated kinases 1 and 2 (ERK1/2) mitogen-activated protein (MAP) kinase (gp130(Y757F/Y757F)) activation to assess the individual contribution of each pathway to macrophage formation. While the inhibition by IL-6 of macrophage colony-stimulating factor (M-CSF)-induced colony formation observed in gp130(wt/wt) mice was abolished in gp130(Delta STAT/Delta STAT) mice, inhibition of macrophage colony formation was enhanced in gp130(Y757F/Y757F) mice. In gp130(Delta STAT/Delta STAT) bone marrow-derived macrophages (BMMs), both IL-6- and M-CSF-induced ERK1/2 tyrosine phosphorylation was enhanced. By contrast, tyrosine phosphorylation of ERK1/2 in response to M-CSF was reduced in gp130(Y757F/Y757F) BMMs, and the pattern of ERK1/2 activation in gp130 mutant BMMs correlated with their opposing responsiveness to M-CSF-induced proliferation. When compared to the level of expression in gp130(wt/wt) BMMs, c-fms expression was elevated in gp130(Delta STAT/Delta STAT) BMMs but reduced in gp130(Y757F/Y757F) BMMs. Finally, an ERK1/2 inhibitor suppressed M-CSF-induced BMM proliferation, and this result corresponded to a reduction in c-fms expression. Collectively, these results provide a functional and causal correlation between gp130-dependent ERK MAP kinase signaling and c-fms gene activation, a finding that provides a potential mechanism underlying the inhibition of M-CSF-dependent macrophage development by IL-6 family cytokines in mice.
dc.formatapplication/pdf
dc.languageEnglish
dc.publisherAMER SOC MICROBIOLOGY
dc.subjectOncology and Carcinogenesis; Cancer and Related Disorders
dc.titleImbalanced gp130-dependent signaling in macrophages alters macrophage colony-stimulating factor responsiveness via regulation of c-fms expression
dc.typeJournal Article
dc.identifier.doi10.1128/MCB.24.4.1453-1463.2004
melbourne.peerreviewPeer Reviewed
melbourne.affiliationThe University of Melbourne
melbourne.affiliation.departmentSurgery - Royal Melbourne And Western Hospital
melbourne.source.titleMOLECULAR AND CELLULAR BIOLOGY
melbourne.source.volume24
melbourne.source.issue4
melbourne.source.pages1453-1463
melbourne.publicationid29218
melbourne.elementsid263735
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC344172
melbourne.contributor.authorBozinovski, Steven
melbourne.contributor.authorErnst, Matthias
melbourne.contributor.authorJENKINS, BRENDAN
dc.identifier.eissn1098-5549
melbourne.accessrightsAccess this item via the Open Access location


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