Smad2 transduces common signals from receptor serine-threonine and tyrosine kinases

被引：251

作者：

de Caestecker, MP

Parks, WT

Frank, CJ

Castagnino, P

Bottaro, DP

Roberts, AB

Lechleider, RJ ^{[1
]}

机构：

[1] NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA

[2] NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA

来源：

GENES & DEVELOPMENT | 1998年 / 12卷 / 11期

关键词：

SMAD; TGF-beta; signal transduction; protein phosphorylation; HGF; receptor kinases;

D O I：

10.1101/gad.12.11.1587

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

SMAD proteins mediate signals from receptor serine-threonine kinases (RSKs) of the TGP-beta superfamily. We demonstrate here that HGF and EGF, which signal through RTKs, can also mediate SMAD-dependent reporter gene activation and induce rapid phosphorylation of endogenous SMAD proteins by kinase(s) downstream of MEK1. HGF induces phosphorylation and nuclear translocation of epitope-tagged Smad2 and a mutation that blocks TGF-beta signaling also blocks HGF signal transduction. Smad2 may thus act as a common positive effector of TGE-beta- and HGF-induced signals and serve to modulate cross talk between RTK and RSK signaling pathways.

引用

收藏

页码：1587 / 1592

页数：6

相关论文

共 38 条

[1] T beta RI phosphorylation of Smad2 on Ser(465) and Ser(467) is required for Smad2-Smad4 complex formation and signaling [J].

Abdollah, S ;

MaciasSilva, M ;

Tsukazaki, T ;

Hayashi, H ;

Attisano, L ;

Wrana, JL .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (44) :27678-27685

[2] AN ASSAY FOR TRANSFORMING GROWTH-FACTOR-BETA USING CELLS TRANSFECTED WITH A PLASMINOGEN-ACTIVATOR INHIBITOR-1 PROMOTER LUCIFERASE CONSTRUCT [J].

ABE, M ;

HARPEL, JG ;

METZ, CN ;

NUNES, I ;

LOSKUTOFF, DJ ;

RIFKIN, DB .

ANALYTICAL BIOCHEMISTRY, 1994, 216 (02) :276-284

[3]

Cantley LC, 1997, ADV SEC MESS PHOSPH, V31, P41

[4] Smad4 and FAST-1 in the assembly of activin-responsive factor [J].

Chen, X ;

Weisberg, E ;

Fridmacher, V ;

Watanabe, M ;

Naco, G ;

Whitman, M .

NATURE, 1997, 389 (6646) :85-89

[5] Hepatocyte growth factor (HGF)/NK1 is a naturally occurring HGF scatter factor variant with partial agonist antagonist activity [J].

Cioce, V ;

Csaky, KG ;

Chan, AML ;

Bottaro, DP ;

Taylor, WG ;

Jensen, R ;

Aaronson, SA ;

Rubin, JS .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (22) :13110-13115

[6] The mitogenic and myogenic actions of insulin-like growth factors utilize distinct signaling pathways [J].

Coolican, SA ;

Samuel, DS ;

Ewton, DZ ;

McWade, FJ ;

Florini, JR .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (10) :6653-6662

[7] Characterization of functional domains within Smad4/DPC4 [J].

deCaestecker, MP ;

Hemmati, P ;

LarischBloch, S ;

Ajmera, R ;

Roberts, AB ;

Lechleider, RJ .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (21) :13690-13696

[8] DPC4 (SMAD4) mediates transforming growth factor-beta 1 (TGF-beta 1) induced growth inhibition and transcriptional response in breast tumour cells [J].

deWinter, JP ;

Roelen, BAJ ;

tenDijke, P ;

vanderBurg, B ;

vandenEijndenvanRaaij, A .

ONCOGENE, 1997, 14 (16) :1891-1899

[9]

FRENZ DA, 1994, DEVELOPMENT, V120, P415

[10] Altered transforming growth factor beta signaling in epithelial cells when Ras activation is blocked [J].

Hartsough, MT ;

Frey, RS ;

Zipfel, PA ;

Buard, A ;

Cook, SJ ;

McCormick, F ;

Mulder, KM .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (37) :22368-22375

← 1 2 3 4 →