QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online December 30, 2003
doi: 10.1242/10.1242/dev.00927

This Article Figures Only Full Text Full Text (PDF) Supplemental Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development 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 Zhukovskaya,, N. V. Articles by Williams, J. G. Search for Related Content PubMed PubMed Citation Articles by Zhukovskaya,, N. V. Articles by Williams, J. G. Social Bookmarking                         What's this?

Dd-STATb, a Dictyostelium STAT protein with a highly aberrant SH2 domain, functions as a regulator of gene expression during growth and early development

Natasha V. Zhukovskaya,^1,*, Masashi Fukuzawa,^1,*, Masatsune Tsujioka¹, Keith A. Jermyn¹, Takefumi Kawata¹, Tomoaki Abe¹, Marketa Zvelebil² and Jeffrey G. Williams

¹ School of Life Sciences, University of Dundee, MSI/WTB Complex, Dow Street, Dundee DD1 5EH, UK
² University College London, Ludwig Institute for Cancer Research, The Cruciform Building, Gower Street, London WC1E 6BT, UK

Author for correspondence (e-mail: j.g.williams{at}dundee.ac.uk)

Accepted 16 October 2003

Dictyostelium, the only known non-metazoan organism to employ SH2 domain:phosphotyrosine signaling, possesses STATs (signal transducers and activators of transcription) and protein kinases with orthodox SH2 domains. Here, however, we describe a novel Dictyostelium STAT containing a remarkably divergent SH2 domain. Dd-STATb displays a 15 amino acid insertion in its SH2 domain and the conserved and essential arginine residue, which interacts with phosphotyrosine in all other known SH2 domains, is substituted by leucine. Despite these abnormalities, Dd-STATb is biologically functional. It has a subtle role in growth, so that Dd-STATb-null cells are gradually lost from the population when they are co-cultured with parental cells, and microarray analysis identified several genes that are either underexpressed or overexpressed in the Dd-STATb null strain. The best characterised of these, discoidin 1, is a marker of the growth-development transition and it is overexpressed during growth and early development of Dd-STATb null cells. Dimerisation of STAT proteins occurs by mutual SH2 domain:phosphotyrosine interactions and dimerisation triggers STAT nuclear accumulation. Despite its aberrant SH2 domain, the Dd-STATb protein sediments at the size expected for a homodimer and it is constitutively enriched in the nucleus. Moreover, these properties are retained when the predicted site of tyrosine phosphorylation is substituted by phenylalanine. These observations suggest a non-canonical mode of activation of Dd-STATb that does not rely on orthodox SH2 domain:phosphotyrosine interactions.

Key words: Dictyostelium, STAT (signal transducer and activator of transcription) protein, SH2 domain:phosphotyrosine interaction, Growth control, Discoidin 1

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

Related articles in Development:

A different STATus quo in Dictyostelium

Development 2004 131: 203. [Full Text]  

This article has been cited by other articles:

				D. Pincus, I. Letunic, P. Bork, and W. A. Lim From the Cover: Evolution of the phospho-tyrosine signaling machinery in premetazoan lineages PNAS, July 15, 2008; 105(28): 9680 - 9684. [Abstract] [Full Text] [PDF]

				Y. Wang and D. E. Levy C. elegans STAT: evolution of a regulatory switch FASEB J, August 1, 2006; 20(10): 1641 - 1652. [Abstract] [Full Text] [PDF]

				R. Wang, P. Cherukuri, and J. Luo Activation of Stat3 Sequence-specific DNA Binding and Transcription by p300/CREB-binding Protein-mediated Acetylation J. Biol. Chem., March 25, 2005; 280(12): 11528 - 11534. [Abstract] [Full Text] [PDF]

				Z.-l. Yuan, Y.-j. Guan, D. Chatterjee, and Y. E. Chin Stat3 Dimerization Regulated by Reversible Acetylation of a Single Lysine Residue Science, January 14, 2005; 307(5707): 269 - 273. [Abstract] [Full Text] [PDF]