Heregulin degradation in the absence of rapid receptor-mediated internalization

被引:38
作者
Baulida, J
Carpenter, G
机构
[1] VANDERBILT UNIV, SCH MED, DEPT BIOCHEM, NASHVILLE, TN 37232 USA
[2] VANDERBILT UNIV, SCH MED, DEPT MED, NASHVILLE, TN 37232 USA
关键词
EPIDERMAL GROWTH-FACTOR; KINASE-C PHOSPHORYLATION; EGF RECEPTOR; HUMAN-FIBROBLASTS; 3T3; CELLS; PROTEIN; BINDING; TRANSFORMATION; ENDOCYTOSIS;
D O I
10.1006/excr.1997.3515
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Heregulin receptors are unable to mediate the rapid internalization of bound ligand as demonstrated in cells transfected with chimeric or wild-type ErbB-2, -3, or -4 receptors (Baulida ct al., 1996, J. Biol. Chem. 271, 5251-5257; Pinkas-Kramanski ct al., 1996, EMBO J. 15, 2452-2467). This observation is now extended to include mammary carcinoma cell lines (SK-BR-3 and MDA-543) which express endogenous ErbB-S and ErbB-3 receptors. Also, the fate of receptor-bound heregulin is examined. While receptor-bound heregulin is not rapidly internalized, the ligand is subject to a slow process of inactivation and degradation, which requires heregulin incubation at 37 degrees C with cells that express heregulin receptors. The degradation of heregulin is blocked to a significant extent by chloroquine, an inhibitor of endosome fusion with lysosomes, indicating that heregulin is slowly internalized and degraded. However, this process is not sufficiently rapid to produce ligand-dependent down-regulation of heregulin receptors. (C) 1997 Academic Press.
引用
收藏
页码:167 / 172
页数:6
相关论文
共 25 条
[1]  
Baulida J, 1996, J BIOL CHEM, V271, P5251
[2]   COLCHICINE INHIBITS EPIDERMAL GROWTH-FACTOR DEGRADATION IN 3T3 CELLS [J].
BROWN, KD ;
FRIEDKIN, M ;
ROZENGURT, E .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1980, 77 (01) :480-484
[3]  
CAO HN, 1991, ONCOGENE, V6, P705
[4]   I125 LABELED HUMAN EPIDERMAL GROWTH-FACTOR - BINDING, INTERNALIZATION, AND DEGRADATION IN HUMAN FIBROBLASTS [J].
CARPENTER, G ;
COHEN, S .
JOURNAL OF CELL BIOLOGY, 1976, 71 (01) :159-171
[6]   OVEREXPRESSION OF THE HUMAN EGF RECEPTOR CONFERS AN EGF-DEPENDENT TRANSFORMED PHENOTYPE TO NIH 3T3 CELLS [J].
DIFIORE, PP ;
PIERCE, JH ;
FLEMING, TP ;
HAZAN, R ;
ULLRICH, A ;
KING, CR ;
SCHLESSINGER, J ;
AARONSON, SA .
CELL, 1987, 51 (06) :1063-1070
[7]   HETERODIMERIZATION AND FUNCTIONAL INTERACTION BETWEEN EGF RECEPTOR FAMILY MEMBERS - A NEW SIGNALING PARADIGM WITH IMPLICATIONS FOR BREAST-CANCER RESEARCH [J].
EARP, HS ;
DAWSON, TL ;
LI, X ;
YU, H .
BREAST CANCER RESEARCH AND TREATMENT, 1995, 35 (01) :115-132
[8]   KINETICS OF EPIDERMAL GROWTH-FACTOR BINDING AND PROCESSING IN ISOLATED INTACT RAT HEPATOCYTES - DYNAMIC EXTERNALIZATION OF RECEPTORS DURING LIGAND INTERNALIZATION [J].
GLADHAUG, IP ;
CHRISTOFFERSEN, T .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1987, 164 (02) :267-275
[9]   PROTEIN KINASE-C PHOSPHORYLATION OF THE EGF RECEPTOR AT A THREONINE RESIDUE CLOSE TO THE CYTOPLASMIC FACE OF THE PLASMA-MEMBRANE [J].
HUNTER, T ;
LING, N ;
COOPER, JA .
NATURE, 1984, 311 (5985) :480-483
[10]   PROTEIN-KINASE-C PHOSPHORYLATION AT THR-654 OF THE UNOCCUPIED EGF RECEPTOR AND EGF BINDING REGULATE FUNCTIONAL RECEPTOR LOSS BY INDEPENDENT MECHANISMS [J].
LIN, CR ;
CHEN, WS ;
LAZAR, CS ;
CARPENTER, CD ;
GILL, GN ;
EVANS, RM ;
ROSENFELD, MG .
CELL, 1986, 44 (06) :839-848