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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| Format: | Article |
| Language: | English |
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BMC
2002-01-01
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| Series: | Biological Research |
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| Online Access: | http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602002000200022 |
| _version_ | 1811215511765123072 |
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| author | GEORGE THOMAS |
| author_facet | GEORGE THOMAS |
| author_sort | GEORGE THOMAS |
| collection | DOAJ |
| 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>). |
| first_indexed | 2024-04-12T06:23:49Z |
| format | Article |
| id | doaj.art-8cab4683acfd4034b8970fa2627d02bf |
| institution | Directory Open Access Journal |
| issn | 0716-9760 0717-6287 |
| language | English |
| last_indexed | 2024-04-12T06:23:49Z |
| publishDate | 2002-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Biological Research |
| spelling | doaj.art-8cab4683acfd4034b8970fa2627d02bf2022-12-22T03:44:13ZengBMCBiological Research0716-97600717-62872002-01-01352305313The S6 kinase Signaling Pathway In The Control of Development and GrowthGEORGE THOMASThe 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>).http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602002000200022DrosophilaßcellsDiabetes |
| spellingShingle | GEORGE THOMAS The S6 kinase Signaling Pathway In The Control of Development and Growth Biological Research Drosophila ßcells Diabetes |
| title | 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_short | 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 |
| topic | Drosophila ßcells Diabetes |
| url | http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602002000200022 |
| work_keys_str_mv | AT georgethomas thes6kinasesignalingpathwayinthecontrolofdevelopmentandgrowth AT georgethomas s6kinasesignalingpathwayinthecontrolofdevelopmentandgrowth |