Concerted regulation of nuclear and cytoplasmic activities of SR proteins by AKT

被引：191

作者：

Blaustein, M

Pelisch, F

Tanos, T

Muñoz, MJ

Wengier, D

Quadrana, L

Sanford, JR

Muschietti, JP

Kornblihtt, AR

Cáceres, JF

Coso, OA

Srebrow, A

机构：

[1] Univ Buenos Aires, Fac Ciencias Exactas & Nat, Lab Fisiol & Biol Mol,Dept Fisiol Biol Mol & Celu, CONICET,Inst Fisiol Biol Mol & Neurociencias, Buenos Aires, DF, Argentina

[2] Univ Buenos Aires, Fac Ciencias Exactas & Nat, Dept Fisiol Biol Mol & Celular, CONICET,Inst Ingn Genet & Biol Mol, RA-1428 Buenos Aires, DF, Argentina

[3] Western Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2005年 / 12卷 / 12期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1038/nsmb1020

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Serine/arginine-rich (SR) proteins are important regulators of mRNA splicing. Several postsplicing activities have been described for a subset of shuttling SR proteins, including regulation of mRNA export and translation. Using the fibronectin gene to study the links between signal-transduction pathways and SR protein activity, we show that growth factors not only modify the alternative splicing pattern of the fibronectin gene but also alter translation of reporter messenger RNAs in an SR protein-dependent fashion, providing two coregulated levels of isoform-specific amplification. These effects are inhibited by specific small interfering RNAs against SR proteins and are mediated by the AKT kinase, which elicits opposite effects to those evoked by overexpressing SR protein kinases Clk and SRPK. These results show how SR protein activity is modified in response to extracellular stimulation, leading to a concerted regulation of splicing and translation.

引用

页码：1037 / 1044

页数：8

共 49 条

[1] Transduction of interleukin-2 antiapoptotic and proliferative signals via Akt protein kinase [J].

Ahmed, NN ;

Grimes, HL ;

Bellacosa, A ;

Chan, TO ;

Tsichlis, PN .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (08) :3627-3632

[2] Mammary epithelial-mesenchymal interaction regulates fibronectin alternative splicing via phosphatidylinositol 3-kinase [J].

Blaustein, M ;

Pelisch, F ;

Coso, OA ;

Bissell, MJ ;

Kornblihtt, AR ;

Srebrow, A .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (20) :21029-21037

[3]

BOS JL, 1989, CANCER RES, V49, P4682

[4]

Bourgeois CF, 1999, MOL CELL BIOL, V19, P7347

[5] RNA folding affects the recruitment of SR proteins by mouse and human polypurinic enhancer elements in the fibronectin EDA dxon [J].

Buratti, E ;

Muro, AF ;

Giombi, M ;

Gherbassi, D ;

Iaconcig, A ;

Baralle, FE .

MOLECULAR AND CELLULAR BIOLOGY, 2004, 24 (03) :1387-1400

[6] Role of the modular domains of SR proteins in subnuclear localization and alternative splicing specificity [J].

Caceres, JF ;

Misteli, T ;

Screaton, GR ;

Spector, DL ;

Krainer, AR .

JOURNAL OF CELL BIOLOGY, 1997, 138 (02) :225-238

[7] A specific subset of SR proteins shuttles continuously between the nucleus and the cytoplasm [J].

Cáceres, JF ;

Screaton, GR ;

Krainer, AR .

GENES & DEVELOPMENT, 1998, 12 (01) :55-66

[8] A NOVEL BIPARTITE SPLICING ENHANCER MODULATES THE DIFFERENTIAL PROCESSING OF THE HUMAN FIBRONECTIN EDA EXON [J].

CAPUTI, M ;

CASARI, G ;

GUENZI, S ;

TAGLIABUE, R ;

SIDOLI, A ;

MELO, CA ;

BARALLE, FE .

NUCLEIC ACIDS RESEARCH, 1994, 22 (06) :1018-1022

[9] The splicing factors 9G8 and SRp20 transactivate splicing through different and specific enhancers [J].

Cavaloc, Y ;

Bourgeois, CF ;

Kister, L ;

Stévenin, J .

RNA, 1999, 5 (03) :468-483

[10] The Clk/Sty protein kinase phosphorylates SR splicing factors and regulates their intranuclear distribution [J].

Colwill, K ;

Pawson, T ;

Andrews, B ;

Prasad, J ;

Manley, JL ;

Bell, JC ;

Duncan, PI .

EMBO JOURNAL, 1996, 15 (02) :265-275

← 1 2 3 4 5 →