THE TYROSINE KINASE INHIBITOR TYRPHOSTIN BLOCKS THE CELLULAR ACTIONS OF NERVE GROWTH-FACTOR

被引:114
作者
OHMICHI, M
PANG, L
RIBON, V
GAZIT, A
LEVITZKI, A
SALTIEL, AR
机构
[1] WARNER LAMBERT PARKE DAVIS,PARKE DAVIS PHARMACEUT RES DIV,DEPT SIGNAL TRANSDUCT,ANN ARBOR,MI 48105
[2] UNIV MICHIGAN,SCH MED,DEPT PHYSIOL,ANN ARBOR,MI 48109
[3] HEBREW UNIV JERUSALEM,DEPT BIOL CHEM,IL-91904 JERUSALEM,ISRAEL
关键词
D O I
10.1021/bi00068a024
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
A series of the synthetic protein kinase inhibitors known as tyrphostins were examined for their effects on the tyrosine autophosphorylation of the pp140c-trk, nerve growth factor (NGF) receptor. One of the tyrphostins, AG879, inhibited NGF-dependent pp140c-trk tyrosine phosphorylation, but did not affect tyrosine phosphorylation of epidermal growth factor or platelet-derived growth factor receptors. In addition, the tyrosine phosphorylation of the receptor-associated protein pp38 was also attenuated by the tyrphostin. This effect was time- and dose-dependent, although inhibition of pp38 phosphorylation occurred earlier and at lower concentrations of the compound. AG879 also inhibited NGF-induced PLC-gamma1 phosphorylation, phosphatidylinositol-3 (PI3) kinase activation, the association of the tyrosine-phosphorylated proteins pp100 and pp110 with the p85 subunit of PI-3 kinase, mitogen activated protein and raf-1 kinases, and c-fos induction. In addition, AG879 inhibited NGF-induced neurite outgrowth in PC12 cells. These data indicate that tyrosine kinase activity of the pp140c-trk NGF receptor is essential for the cellular actions of this growth factor.
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页码:4650 / 4658
页数:9
相关论文
共 52 条
[41]   ACTIVATION OF PHOSPHATIDYLINOSITOL-3 KINASE BY NERVE GROWTH-FACTOR INVOLVES INDIRECT COUPLING OF THE TRK PROTOONCOGENE WITH SRC HOMOLOGY-2 DOMAINS [J].
OHMICHI, M ;
DECKER, SJ ;
SALTIEL, AR .
NEURON, 1992, 9 (04) :769-777
[42]   NERVE GROWTH-FACTOR INDUCES THE ASSOCIATION OF A 130-KD PHOSPHOPROTEIN WITH ITS RECEPTOR IN PC-12 PHEOCHROMOCYTOMA CELLS [J].
OHMICHI, M ;
DECKER, SJ ;
SALTIEL, AR .
CELL REGULATION, 1991, 2 (09) :691-697
[43]  
OHMICHI M, 1992, J BIOL CHEM, V267, P21601
[44]  
OHMICHI M, 1992, J BIOL CHEM, V267, P14604
[45]   NERVE GROWTH-FACTOR BINDS TO THE 140 KD TRK PROTOONCOGENE PRODUCT AND STIMULATES ITS ASSOCIATION WITH THE SRC HOMOLOGY DOMAIN OF PHOSPHOLIPASE-C-GAMMA-1 [J].
OHMICHI, M ;
DECKER, SJ ;
PANG, L ;
SALTIEL, AR .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1991, 179 (01) :217-223
[46]   TYRPHOSTINS INHIBIT THE EPIDERMAL GROWTH-FACTOR RECEPTOR-MEDIATED BREAKDOWN OF PHOSPHOINOSITIDES [J].
POSNER, I ;
GAZIT, A ;
GILON, C ;
LEVITZKI, A .
FEBS LETTERS, 1989, 257 (02) :287-291
[47]  
RAWLAND EA, 1987, J BIOL CHEM, V262, P7504
[48]   DIVERSITY IN CELLULAR SIGNALING FOR NERVE GROWTH-FACTOR AND INSULIN - VARIATIONS ON A COMMON THEME [J].
SALTIEL, AR ;
DECKER, SJ .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 1991, 81 (1-3) :C197-C202
[49]  
TAPLEY P, 1992, ONCOGENE, V7, P371
[50]   HYBRIDIZATION OF DENATURED RNA AND SMALL DNA FRAGMENTS TRANSFERRED TO NITROCELLULOSE [J].
THOMAS, PS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1980, 77 (09) :5201-5205