Please use this identifier to cite or link to this item: https://doi.org/10.1210/me.2008-0260
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dc.titleA preformed signaling complex mediates GnRH-activated ERK phosphorylation of paxillin and FAK at focal adhesions in LβT2 gonadotrope cells
dc.contributor.authorDobkin-Bekman, M.
dc.contributor.authorNaidich, M.
dc.contributor.authorRahamim, L.
dc.contributor.authorPrzedecki, F.
dc.contributor.authorAlmog, T.
dc.contributor.authorLim, S.
dc.contributor.authorMelamed, P.
dc.contributor.authorLiu, P.
dc.contributor.authorWohland, T.
dc.contributor.authorYao, Z.
dc.contributor.authorSeger, R.
dc.contributor.authorNaor, Z.
dc.date.accessioned2014-06-23T05:30:47Z
dc.date.available2014-06-23T05:30:47Z
dc.date.issued2009-11
dc.identifier.citationDobkin-Bekman, M., Naidich, M., Rahamim, L., Przedecki, F., Almog, T., Lim, S., Melamed, P., Liu, P., Wohland, T., Yao, Z., Seger, R., Naor, Z. (2009-11). A preformed signaling complex mediates GnRH-activated ERK phosphorylation of paxillin and FAK at focal adhesions in LβT2 gonadotrope cells. Molecular Endocrinology 23 (11) : 1850-1864. ScholarBank@NUS Repository. https://doi.org/10.1210/me.2008-0260
dc.identifier.issn08888809
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/75472
dc.description.abstractMost receptor tyrosine kinases and G protein-coupled receptors (GPCRs) operate via a limited number of MAPK cascades but still exert diverse functions, and therefore signal specificity remains an enigma. Also, most GPCR ligands utilize families of receptors for mediation of diverse biological actions; however, the mammalian type I GnRH receptor (GnRHR) seems to be the sole receptor mediating GnRH-induced gonadotropin synthesis and release. Signaling complexes associated with GPCRs may thus provide the means for signal specificity. Here we describe a signaling complex associated with the GnRHR, which is a unique GPCR lacking a C-terminal tail. Unlike other GPCRs, this signaling complex is preformed, and exposure of LβT2 gonadotropes to GnRH induces its dynamic rearrangement. The signaling complex includes c-Src, protein kinase Cδ, -ε, and -α, Ras, MAPK kinase 1/2, ERK1/2, tubulin, focal adhesion kinase (FAK), paxillin, vinculin, caveolin-1, kinase suppressor of Ras-1, and the GnRHR. Exposure to GnRH (5 min) causes MAPK kinase 1/2, ERK1/2, tubulin, vinculin, and the GnRHR to detach from c-Src, but they reassociate within 30 min. On the other hand, FAK, paxillin, the protein kinase Cs, and caveolin-1 stay bound to c-Src, whereas kinase suppressor of Ras-1 appears in the complex only 30 min after GnRH stimulation. GnRH was found to activate ERK1/2 in the complex in a c-Src-dependent manner, and the activated ERK1/2 subsequently phosphorylates FAK and paxillin. In parallel, caveolin-1, FAK, vinculin, and paxillin are phosphorylated on Tyr residues apparently by GnRH-activated c-Src. Receptor tyrosine kinases and GPCRs translocate ERK1/2 to the nucleus to phosphorylate and activate transcription factors. We therefore propose that the role of the multiprotein signaling complex is to sequester a cytosolic pool of activated ERK1/2 to phosphorylate FAK and paxillin at focal adhesions. Copyright © 2009 by The Endocrine Society.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1210/me.2008-0260
dc.sourceScopus
dc.typeArticle
dc.contributor.departmentBIOLOGICAL SCIENCES
dc.contributor.departmentCHEMISTRY
dc.description.doi10.1210/me.2008-0260
dc.description.sourcetitleMolecular Endocrinology
dc.description.volume23
dc.description.issue11
dc.description.page1850-1864
dc.description.codenMOENE
dc.identifier.isiut000271210800011
Appears in Collections:Staff Publications

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