The G3 domain of versican enhances cell proliferation via epidermal growth factor-like motifs

被引:131
作者
Zhang, Y
Cao, L
Yang, BL
Yang, BB
机构
[1] Univ Toronto, Sunnybrook Hlth Sci Ctr, Trauma Res Program, Toronto, ON M4N 3M5, Canada
[2] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Lab Med & Pathobiol, Toronto, ON M4N 3M5, Canada
关键词
D O I
10.1074/jbc.273.33.21342
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
Versican is a member of the large aggregating chondroitin sulfate proteoglycan family. We have expressed in NIH3T3 fibroblasts a recombinant versican mini-gene comprising the G1 and G3 domains and 15% of the CS domain. We observed that expression of the mini-versican gene stimulated cell proliferation as determined by cell counting and cell cycle analysis. Addition of exogenous mini-versican protein to cultured cells produced the same result. The effects of the mini-versican were greatly reduced when the G3 domain was deleted. Expression of the G3 domain alone promotes cell proliferation, and addition of purified G3 gene products to NIH3T3 fibroblasts and cultured chicken fibroblasts enhances cell growth. Further, deletion of the epidermal growth factor (EGF)-like motifs in the versican G3 domain reduced the effects of the mini-versican on cell proliferation. In the presence of the purified mini-versican protein, antisense oligonucleotides to the EGF receptor inhibited proliferation of NIH3T3 fibroblasts, compared with control sense oligonucleotides. Taken together, these results imply that versican enhances cell proliferation, and this effect is mediated, at least in part, by the action of versican EGF-like motifs on endogenous EGF receptor.
引用
收藏
页码:21342 / 21351
页数:10
相关论文
共 41 条
[11]  
DOURSZIMMERMANN MT, 1994, J BIOL CHEM, V269, P32992
[12]   ASSOCIATION OF VERSICAN WITH DERMAL MATRICES AND ITS POTENTIAL ROLE IN HAIR FOLLICLE DEVELOPMENT AND CYCLING [J].
DUCROS, DL ;
LEBARON, RG ;
COUCHMAN, JR .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1995, 105 (03) :426-431
[13]   LIPOFECTION - A HIGHLY EFFICIENT, LIPID-MEDIATED DNA-TRANSFECTION PROCEDURE [J].
FELGNER, PL ;
GADEK, TR ;
HOLM, M ;
ROMAN, R ;
CHAN, HW ;
WENZ, M ;
NORTHROP, JP ;
RINGOLD, GM ;
DANIELSEN, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (21) :7413-7417
[14]   THE EPIDERMAL GROWTH FACTOR-LIKE DOMAIN OF RECOMBINANT HUMAN THROMBOMODULIN EXHIBITS MITOGENIC ACTIVITY FOR SWISS 3T3 CELLS [J].
HAMADA, H ;
ISHII, H ;
SAKYO, K ;
HORIE, S ;
NISHIKI, K ;
KAZAMA, M .
BLOOD, 1995, 86 (01) :225-233
[15]   MAPPING OF THE VERSICAN PROTEOGLYCAN GENE (CSPG2) TO THE LONG ARM OF HUMAN CHROMOSOME-5 (5Q12-5Q14) [J].
IOZZO, RV ;
NASO, MF ;
CANNIZZARO, LA ;
WASMUTH, JJ ;
MCPHERSON, JD .
GENOMICS, 1992, 14 (04) :845-851
[16]  
KIMATA K, 1986, J BIOL CHEM, V261, P3517
[17]  
KRUSIUS T, 1987, J BIOL CHEM, V262, P13120
[18]  
LANDOLT RM, 1995, DEVELOPMENT, V121, P2303
[19]  
LEBARON RG, 1992, J BIOL CHEM, V267, P10003
[20]   THE MOUSE WAVED-2 PHENOTYPE RESULTS FROM A POINT MUTATION IN THE EGF RECEPTOR TYROSINE KINASE [J].
LUETTEKE, NC ;
PHILLIPS, HK ;
QIU, TH ;
COPELAND, NG ;
EARP, HS ;
JENKINS, NA ;
LEE, DC .
GENES & DEVELOPMENT, 1994, 8 (04) :399-413