IDENTIFICATION OF A COMPETITIVE HGF ANTAGONIST ENCODED BY AN ALTERNATIVE TRANSCRIPT

被引:209
作者
CHAN, AML [1 ]
RUBIN, JS [1 ]
BOTTARO, DP [1 ]
HIRSCHFIELD, DW [1 ]
CHEDID, M [1 ]
AARONSON, SA [1 ]
机构
[1] NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892
关键词
D O I
10.1126/science.1720571
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We identified a naturally occurring hepatocyte growth factor (HGF) variant, whose predicted sequence extends only through the second kringle domain of this plasminogen-related molecule. This smaller molecule, derived from an alternative HGF transcript, lacked mitogenic activity but specifically inhibited HGF-induced mitogenesis. Cross-linking studies demonstrated that the truncated molecule competes with HGF for binding to the HGF receptor, which has been identified as the c-met proto-oncogene product. Thus, the same gene encodes both a growth factor and its direct antagonist.
引用
收藏
页码:1382 / 1385
页数:4
相关论文
共 37 条
  • [1] IDENTIFICATION OF THE HEPATOCYTE GROWTH-FACTOR RECEPTOR AS THE C-MET PROTOONCOGENE PRODUCT
    BOTTARO, DP
    RUBIN, JS
    FALETTO, DL
    CHAN, AML
    KMIECIK, TE
    VANDEWOUDE, GF
    AARONSON, SA
    [J]. SCIENCE, 1991, 251 (4995) : 802 - 804
  • [2] PURIFICATION, CLONING, EXPRESSION AND BIOLOGICAL CHARACTERIZATION OF AN INTERLEUKIN-1 RECEPTOR ANTAGONIST PROTEIN
    CARTER, DB
    DEIBEL, MR
    DUNN, CJ
    TOMICH, CSC
    LABORDE, AL
    SLIGHTOM, JL
    BERGER, AE
    BIENKOWSKI, MJ
    SUN, FF
    MCEWAN, RN
    HARRIS, PKW
    YEM, AW
    WASZAK, GA
    CHOSAY, JG
    SIEU, LC
    HARDEE, MM
    ZURCHERNEELY, HA
    REARDON, IM
    HEINRIKSON, RL
    TRUESDELL, SE
    SHELLY, JA
    EESSALU, TE
    TAYLOR, BM
    TRACEY, DE
    [J]. NATURE, 1990, 344 (6267) : 633 - 638
  • [3] CHAN AML, 1988, ONCOGENE, V2, P593
  • [4] AMPLIFICATION AND OVEREXPRESSION OF THE MET GENE IN SPONTANEOUSLY TRANSFORMED NIH3T3 MOUSE FIBROBLASTS
    COOPER, CS
    TEMPEST, PR
    BECKMAN, MP
    HELDIN, CH
    BROOKES, P
    [J]. EMBO JOURNAL, 1986, 5 (10) : 2623 - 2628
  • [5] Cuatrecasas P, 1976, Adv Protein Chem, V30, P251, DOI 10.1016/S0065-3233(08)60481-7
  • [6] IDENTIFICATION OF A TRUNCATED FORM OF THE NERVE GROWTH-FACTOR RECEPTOR
    DISTEFANO, PS
    JOHNSON, EM
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (01) : 270 - 274
  • [7] PRIMARY STRUCTURE AND FUNCTIONAL EXPRESSION FROM COMPLEMENTARY-DNA OF A HUMAN INTERLEUKIN-1 RECEPTOR ANTAGONIST
    EISENBERG, SP
    EVANS, RJ
    AREND, WP
    VERDERBER, E
    BREWER, MT
    HANNUM, CH
    THOMPSON, RC
    [J]. NATURE, 1990, 343 (6256) : 341 - 346
  • [8] HUMAN KGF IS FGF-RELATED WITH PROPERTIES OF A PARACRINE EFFECTOR OF EPITHELIAL-CELL GROWTH
    FINCH, PW
    RUBIN, JS
    MIKI, T
    RON, D
    AARONSON, SA
    [J]. SCIENCE, 1989, 245 (4919) : 752 - 755
  • [9] Fogh J., 1975, HUMAN TUMOR CELLS IN, P115
  • [10] HEPATOCYTES AND SCATTER FACTOR
    GHERARDI, E
    STOKER, M
    [J]. NATURE, 1990, 346 (6281) : 228 - 228