EPIDERMAL GROWTH-FACTOR AND TRANSFORMING GROWTH FACTOR-ALPHA - DIFFERENTIAL INTRACELLULAR ROUTING AND PROCESSING OF LIGAND-RECEPTOR COMPLEXES

被引:214
作者
EBNER, R [1 ]
DERYNCK, R [1 ]
机构
[1] GENENTECH INC, DEPT DEV BIOL, S SAN FRANCISCO, CA 94080 USA
来源
CELL REGULATION | 1991年 / 2卷 / 08期
关键词
D O I
10.1091/mbc.2.8.599
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Two structurally related but different polypeptide growth factors, epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha), exert their activities after interaction with a common cell-surface EGF/TGF-alpha-receptor. Comparative studies of the effects of both ligands have established that TGF-alpha is more potent than EGF in a variety of biological systems. This observation is not explained by differences in affinities of the ligands for the receptor, because the affinity-constants of both factors are very similar. We have compared the intracellular processing of ligand-receptor complexes using either EGF or TGF-alpha in two different cell systems. We found that TGF-alpha dissociates from the EGF/TGF-alpha-receptor at much higher pH than EGF, which may reflect the substantial difference in the calculated isoelectric points. After internalization, the intracellular TGF-alpha is more rapidly cleared than EGF, and a substantial portion of the released TGF-alpha represents undegraded TGF-alpha in contrast to the mostly degraded EGF. In addition, TGF-alpha did not induce a complete down-regulation of cell surface receptors, as observed with EGF, which is at least in part responsible for a much sooner recovery of the ligand-binding ability after down-regulation, in the case of TGF-alpha. These differences in processing of the ligand-receptor complexes may explain why TGF-alpha exerts quantitatively higher activities than EGF.
引用
收藏
页码:599 / 612
页数:14
相关论文
共 66 条
[31]   PHENYLARSINE OXIDE INDUCED INCREASE IN ALVEOLAR MACROPHAGE SURFACE-RECEPTORS - EVIDENCE FOR FUSION OF INTERNAL RECEPTOR POOLS WITH THE CELL-SURFACE [J].
KAPLAN, J ;
WARD, DM ;
WILEY, HS .
JOURNAL OF CELL BIOLOGY, 1985, 101 (01) :121-129
[32]   GROWTH-STIMULATION OF A431 CELLS BY EPIDERMAL GROWTH-FACTOR - IDENTIFICATION OF HIGH-AFFINITY RECEPTORS FOR EPIDERMAL GROWTH-FACTOR BY AN ANTI-RECEPTOR MONOCLONAL-ANTIBODY [J].
KAWAMOTO, T ;
SATO, JD ;
LE, A ;
POLIKOFF, J ;
SATO, GH ;
MENDELSOHN, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1983, 80 (05) :1337-1341
[33]  
KOBRIN MS, 1986, J BIOL CHEM, V261, P4414
[34]  
KORC M, 1989, J BIOL CHEM, V264, P14990
[35]  
KORC M, 1987, CANCER RES, V47, P4909
[36]   CLEAVAGE OF STRUCTURAL PROTEINS DURING ASSEMBLY OF HEAD OF BACTERIOPHAGE-T4 [J].
LAEMMLI, UK .
NATURE, 1970, 227 (5259) :680-+
[37]   CHICKEN EPIDERMAL GROWTH-FACTOR (EGF) RECEPTOR - CDNA CLONING, EXPRESSION IN MOUSE CELLS, AND DIFFERENTIAL BINDING OF EGF AND TRANSFORMING GROWTH FACTOR-ALPHA [J].
LAX, I ;
JOHNSON, A ;
HOWK, R ;
SAP, J ;
BELLOT, F ;
WINKLER, M ;
ULLRICH, A ;
VENNSTROM, B ;
SCHLESSINGER, J ;
GIVOL, D .
MOLECULAR AND CELLULAR BIOLOGY, 1988, 8 (05) :1970-1978
[38]   INDUCTION OF TRANSFORMING GROWTH FACTOR-ALPHA IN ACTIVATED HUMAN ALVEOLAR MACROPHAGES [J].
MADTES, DK ;
RAINES, EW ;
SAKARIASSEN, KS ;
ASSOIAN, RK ;
SPORN, MB ;
BELL, GI ;
ROSS, R .
CELL, 1988, 53 (02) :285-293
[39]   AFFINITY LABELING OF A TRANSFORMING GROWTH-FACTOR RECEPTOR THAT DOES NOT INTERACT WITH EPIDERMAL GROWTH-FACTOR [J].
MASSAGUE, J ;
CZECH, MP ;
IWATA, K ;
DELARCO, JE ;
TODARO, GJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1982, 79 (22) :6822-6826
[40]  
MASSAGUE J, 1983, J BIOL CHEM, V258, P3614