HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE ADVANCED SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kasai, K. Articles by Arnheiter, H. Search for Related Content PubMed PubMed Citation Articles by Kasai, K. Articles by Arnheiter, H.

¹ Department of Pathology, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan
² Mammalian Development Section, Laboratory of Developmental Neurogenetics, NINDS, NIH, Bethesda, MD 20892, USA
³ Department of Developmental Neurobiology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
⁴ B cell Molecular Biology Section, Laboratory of Immunoregulation, NIAID, NIH, Bethesda, MD 20892, USA

Sonic hedgehog (Shh) is a secreted morphogen crucial for cell fate decision, cellular proliferation, and patterning during vertebrate development. The intracellular Shh signalling is transduced by Smoothened (Smo), a seven-transmembrane spanning protein that belongs to the G-protein coupled receptor family. Among four families of G subunits, Gi has been thought to be responsible for transducing Shh signalling, while several lines of evidence indicated that other signalling pathways may be involved. We found that the G12 family of heterotrimeric G proteins and the small GTPase RhoA are involved in Shh/Smo-mediated cellular responses, including stimulation of target gene promoter and inhibition of neurite outgrowth of neuroblastoma cells. We also found that the G12/RhoA pathway is responsible for Smo-induced nuclear import of GLI3 which is thought to transduce Shh signals to nucleus. Furthermore, misexpression of a G12-specific GTPase-activating protein in rat neural tubes leads to pertubation of motor neurone and interneurone development, mimicking the effects of decreased Shh signalling. These results show that Shh signalling is mediated in part by activating G12 family coupled signalling pathways. The participation of RhoA, a pivotal molecular switch in many signal transduction pathways, may help explain how Shh can trigger a variety of cellular responses.

^* Correspondence: E-mail: kkasai{at}amugw.aichi-med-u.ac.jp

This article has been cited by other articles:

				K. Kasai, S. Inaguma, A. Yoneyama, K. Yoshikawa, and H. Ikeda SCL/TAL1 Interrupting Locus Derepresses GLI1 from the Negative Control of Suppressor-of-Fused in Pancreatic Cancer Cell Cancer Res., October 1, 2008; 68(19): 7723 - 7729. [Abstract] [Full Text] [PDF]

				A. R. Meloni, G. B. Fralish, P. Kelly, A. Salahpour, J. K. Chen, R. J. Wechsler-Reya, R. J. Lefkowitz, and M. G. Caron Smoothened Signal Transduction Is Promoted by G Protein-Coupled Receptor Kinase 2 Mol. Cell. Biol., October 15, 2006; 26(20): 7550 - 7560. [Abstract] [Full Text] [PDF]

				N. A. Riobo, B. Saucy, C. DiLizio, and D. R. Manning Activation of heterotrimeric G proteins by Smoothened PNAS, August 15, 2006; 103(33): 12607 - 12612. [Abstract] [Full Text] [PDF]

				D. Huangfu and K. V. Anderson Signaling from Smo to Ci/Gli: conservation and divergence of Hedgehog pathways from Drosophila to vertebrates Development, January 1, 2006; 133(1): 3 - 14. [Abstract] [Full Text] [PDF]