The α subunit of the G protein G 13 regulates activity of one or more gli transcription factors independently of smoothened

Andrew E. Douglas, Jennifer A. Heim, Feng Shen, Luciana L. Almada, Natalia A. Riobo, Martin E. Fernández-Zapico, David R. Manning

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Smoothened (Smo) is a seven-transmembrane (7-TM) receptor that is essential to most actions of the Hedgehog family of morphogens. We found previously that Smo couples to members of the G i family of heterotrimeric G proteins, which in some cases are integral although alone insufficient in the activation of Gli transcription factors through Hedgehog signaling. In response to a report that the G 12/13 family is relevant to Hedgehog signaling as well, we re-evaluated the coupling ofSmoto one member of this family, G 13, and investigated the capacity of this and other G proteins to activate one or more of forms of Gli. We found no evidence that Smo couples directly to G 13. We found nonetheless that Gα 13 and to some extent Gα q and Gα 12 are able to effect activation of Gli(s). This capacity is realized in some cells, e.g. C3H10T1/2, MC3T3, and pancreatic cancer cells, but not all cells. The mechanism employed is distinct from that achieved through canonical Hedgehog signaling, as the activation does not involve autocrine signaling or in any other way require active Smo and does not necessarily involve enhanced transcription of Gli1. The activation by Gα 13 can be replicated through a G q/G 12/ 13-coupled receptor, CCK A, and is attenuated by inhibitors of p38 mitogen-activated protein kinase and Tec tyrosine kinases. We posit that G proteins, and perhaps G 13 in particular, provide access to Gli that is independent of Smo and that they thus establish a basis for control of at least some forms of Gli-mediated transcription apart from Hedgehogs.

Original languageEnglish (US)
Pages (from-to)30714-30722
Number of pages9
JournalJournal of Biological Chemistry
Volume286
Issue number35
DOIs
StatePublished - Sep 2 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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