The S6 kinase Signaling Pathway In The Control of Development and Growth

The discussion will focus on the role of the ribosomal protein S6 kinase (S6K) signaling pathway in the regulation of cell growth and proliferation. Although 40S ribosomal protein S6 phosphorylation was first described 25 years ago (<A HREF="#20">Gressner and Wool, 1974</A>), i...

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Autor principal:	THOMAS,GEORGE
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2002
Materias:	Drosophila ßcells Diabetes
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602002000200022
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spelling	oai:scielo:S0716-976020020002000222002-12-26The S6 kinase Signaling Pathway In The Control of Development and GrowthTHOMAS,GEORGE Drosophila ßcells Diabetes The discussion will focus on the role of the ribosomal protein S6 kinase (S6K) signaling pathway in the regulation of cell growth and proliferation. Although 40S ribosomal protein S6 phosphorylation was first described 25 years ago (<A HREF="#20">Gressner and Wool, 1974</A>), it only recently has been implicated in the translational up-regulation of mRNAs coding for the components of protein synthetic apparatus (<A HREF="#15">Fumagalli and Thomas, 2000</A>). These mRNAs contain an oligopyrimidine tract at their 5' transcriptional start site, termed a 5'TOP, which has been shown to be essential for their regulation at the translational level (<A HREF="#32">Meyuhas et al., 1996</A>). In parallel, a great deal of information has accumulated concerning the identification of the signaling pathway and the regulatory phosphorylation sites involved in controlling S6K activation (<A HREF="#13">Dufner and Thomas, 1999</A>). Despite this knowledge we are only beginning to identify the direct upstream elements involved in growth factor-induced kinase activation (<A HREF="#9">Dennis et al., 2001</A>; <A HREF="#38">Pullen et al., 1998</A>). Use of the immunosuppressant rapamycin, a bacterial macrolide, in conjunction with dominant interfering and activated forms of S6K1 has helped to establish the role of this signaling cascade in the regulation of growth and proliferation (<A HREF="#11">Dennis and Thomas, 2002</A>). In addition, current studies employing the mouse as well as Drosophila melanogaster have provided new insights into physiological function of S6K in the animal (<A HREF="#33">Montagne et al., 1999</A>; <A HREF="#36">Pende et al., 2000</A>). Loss of dS6K function in Drosophila melanogaster demonstrated its paramount importance in development and growth control (<A HREF="#33">Montagne et al., 1999</A>), whereas deletion of the S6K1 gene in the mouse led to an animal of reduced size and the identification of the S6K1 homologue, S6K2 (<A HREF="#44">Shima et al., 1998</A>). Such mice are significantly smaller during fetal development (<A HREF="#44">Shima et al., 1998</A>) and hypoinsulinemic in the adult, conditions known to lead to type 2 diabetes (<A HREF="#36">Pende et al., 2000</A>).info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.35 n.2 20022002-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602002000200022en10.4067/S0716-97602002000200022
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	Drosophila ßcells Diabetes
spellingShingle	Drosophila ßcells Diabetes THOMAS,GEORGE The S6 kinase Signaling Pathway In The Control of Development and Growth
description	The discussion will focus on the role of the ribosomal protein S6 kinase (S6K) signaling pathway in the regulation of cell growth and proliferation. Although 40S ribosomal protein S6 phosphorylation was first described 25 years ago (<A HREF="#20">Gressner and Wool, 1974</A>), it only recently has been implicated in the translational up-regulation of mRNAs coding for the components of protein synthetic apparatus (<A HREF="#15">Fumagalli and Thomas, 2000</A>). These mRNAs contain an oligopyrimidine tract at their 5' transcriptional start site, termed a 5'TOP, which has been shown to be essential for their regulation at the translational level (<A HREF="#32">Meyuhas et al., 1996</A>). In parallel, a great deal of information has accumulated concerning the identification of the signaling pathway and the regulatory phosphorylation sites involved in controlling S6K activation (<A HREF="#13">Dufner and Thomas, 1999</A>). Despite this knowledge we are only beginning to identify the direct upstream elements involved in growth factor-induced kinase activation (<A HREF="#9">Dennis et al., 2001</A>; <A HREF="#38">Pullen et al., 1998</A>). Use of the immunosuppressant rapamycin, a bacterial macrolide, in conjunction with dominant interfering and activated forms of S6K1 has helped to establish the role of this signaling cascade in the regulation of growth and proliferation (<A HREF="#11">Dennis and Thomas, 2002</A>). In addition, current studies employing the mouse as well as Drosophila melanogaster have provided new insights into physiological function of S6K in the animal (<A HREF="#33">Montagne et al., 1999</A>; <A HREF="#36">Pende et al., 2000</A>). Loss of dS6K function in Drosophila melanogaster demonstrated its paramount importance in development and growth control (<A HREF="#33">Montagne et al., 1999</A>), whereas deletion of the S6K1 gene in the mouse led to an animal of reduced size and the identification of the S6K1 homologue, S6K2 (<A HREF="#44">Shima et al., 1998</A>). Such mice are significantly smaller during fetal development (<A HREF="#44">Shima et al., 1998</A>) and hypoinsulinemic in the adult, conditions known to lead to type 2 diabetes (<A HREF="#36">Pende et al., 2000</A>).
author	THOMAS,GEORGE
author_facet	THOMAS,GEORGE
author_sort	THOMAS,GEORGE
title	The S6 kinase Signaling Pathway In The Control of Development and Growth
title_short	The S6 kinase Signaling Pathway In The Control of Development and Growth
title_full	The S6 kinase Signaling Pathway In The Control of Development and Growth
title_fullStr	The S6 kinase Signaling Pathway In The Control of Development and Growth
title_full_unstemmed	The S6 kinase Signaling Pathway In The Control of Development and Growth
title_sort	s6 kinase signaling pathway in the control of development and growth
publisher	Sociedad de Biología de Chile
publishDate	2002
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602002000200022
work_keys_str_mv	AT thomasgeorge thes6kinasesignalingpathwayinthecontrolofdevelopmentandgrowth AT thomasgeorge s6kinasesignalingpathwayinthecontrolofdevelopmentandgrowth
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The S6 kinase Signaling Pathway In The Control of Development and Growth

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