Chimeric granulocyte/macrophage colony-stimulating factor transforming growth factor-beta (TGF-beta) receptors define a model system for investigating the role of homomeric and heteromeric receptors in TGF-beta signaling

被引:41
作者
Anders, RA
Leof, EB
机构
[1] MAYO CLIN & MAYO FDN,THORAC RES UNIT,ROCHESTER,MN 55905
[2] MAYO CLIN & MAYO FDN,DEPT BIOCHEM & MOL BIOL,ROCHESTER,MN 55905
关键词
D O I
10.1074/jbc.271.36.21758
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
Transforming growth factor-beta (TGF-beta) belongs to a family of ligands that regulate cell growth and differentiation. The most commonly observed receptors are referred to as the type I, type II, and type III (betaglycan) TGF-beta receptors. Two receptor models have been presented to account for the various cellular responses to TGF-beta. The first proposes that all TGF-beta signaling results from the formation of a heteromeric type I/type II complex, while the second suggests that distinct type I or type II TGF-beta receptor combinations mediate aspects of TGF-beta signaling. We have addressed this general question relating to TGF-beta signaling by constructing chimeric receptors consisting of the extracellular domain of the granulocyte/macrophage colony-stimulating factor (GM-CSF) alpha or beta receptor fused to the transmembrane and cytoplasmic domain of the type I or type II TGF-beta receptor. Since high affinity GM-CSF binding requires dimerization of the alpha and beta ligand binding subunits, the response elicited by defined type I and/or type II TGF-beta receptor cytoplasmic domain homomers or heteromers can be examined. We show in mesenchymal AKR-2B cells that while TGF-beta-dependent transient luciferase activity, endogenous gene activity, and longterm biological responses are similarly induced by activating the chimeric heteromeric receptors with GM-CSF as the endogenous TGF-beta receptor, chimeric homomeric type I/type I or type II/type II receptors are signaling-incompetent.
引用
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页码:21758 / 21766
页数:9
相关论文
共 62 条
[11]  
CHEN RH, 1994, J BIOL CHEM, V269, P22868
[12]   INACTIVATION OF THE TYPE-II RECEPTOR REVEALS 2 RECEPTOR PATHWAYS FOR THE DIVERSE TGF-BETA ACTIVITIES [J].
CHEN, RH ;
EBNER, R ;
DERYNCK, R .
SCIENCE, 1993, 260 (5112) :1335-1338
[13]   TGF-BETA-RECEPTOR-MEDIATED SIGNALING [J].
DERYNCK, R .
TRENDS IN BIOCHEMICAL SCIENCES, 1994, 19 (12) :548-553
[14]  
DIJKE PT, 1994, PROG GROWTH FACTOR R, V5, P55
[15]  
DIPERSIO J, 1988, J BIOL CHEM, V263, P1834
[16]  
EBLEN ST, 1995, CANCER RES, V55, P1994
[17]   A GLYCOSYLATION-DEFICIENT ENDOTHELIAL-CELL MUTANT WITH MODIFIED RESPONSES TO TRANSFORMING GROWTH-FACTOR-BETA AND OTHER GROWTH INHIBITORY CYTOKINES - EVIDENCE FOR MULTIPLE GROWTH INHIBITORY SIGNAL TRANSDUCTION PATHWAYS [J].
FAFEUR, V ;
OHARA, B ;
BOHLEN, P .
MOLECULAR BIOLOGY OF THE CELL, 1993, 4 (02) :135-144
[18]   TRANSFORMING GROWTH-FACTOR-BETA (TGF-BETA)-INDUCED DOWN-REGULATION OF CYCLIN-A EXPRESSION REQUIRES A FUNCTIONAL TGF-BETA RECEPTOR COMPLEX - CHARACTERIZATION OF CHIMERIC AND TRUNCATED TYPE-I AND TYPE-II RECEPTORS [J].
FENG, XH ;
FILVAROFF, EH ;
DERYNCK, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (41) :24237-24245
[19]  
FILMUS J, 1992, ONCOGENE, V7, P521
[20]   THE GS DOMAIN OF THE TRANSFORMING GROWTH-FACTOR-BETA TYPE-I RECEPTOR IS IMPORTANT IN SIGNAL-TRANSDUCTION [J].
FRANZEN, P ;
HELDIN, CH ;
MIYAZONO, K .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1995, 207 (02) :682-689