THROMBOPOIETIN, C-MPL LIGAND, INDUCES TYROSINE PHOSPHORYLATION OF TYK2, JAK2, AND STAT3, AND ENHANCES AGONISTS-INDUCED AGGREGATION IN PLATELETS IN-VITRO

被引：132

作者：

EZUMI, Y ^{[1
]}

TAKAYAMA, H ^{[1
]}

OKUMA, M ^{[1
]}

机构：

[1] KYOTO UNIV,FAC MED,DEPT INTERNAL MED,DIV 1,SAKYO KU,KYOTO 606,JAPAN

来源：

FEBS LETTERS | 1995年 / 374卷 / 01期

关键词：

THROMBOPOIETIN; SIGNAL TRANSDUCTION; PROTEIN-TYROSINE KINASE; TRANSCRIPTION FACTOR; PLATELET AGGREGATION; ADENOSINE DIPHOSPHATE;

D O I：

10.1016/0014-5793(95)01072-M

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：

We investigated in vitro effects of recombinant human thrombopoietin (TPO), or c-Mpl ligand, on human platelets, TPO induced rapid dose-dependent tyrosine phosphorylation of several proteins, We identified Janus tyrosine kinases, Tyk2 and JAK2, and a member of STAT (signal transducers and activators of transcription) family, STAT3, as the tyrosine-phosphorylated proteins in response to TPO. TPO by itself did not cause platelet aggregation and shape change, but augmented ADP-induced aggregation in a dose-dependent manner, Acetylsalicylic acid inhibited the secondary aggregation enhanced by TPO, but not the TPO-induced potentiation of the primary aggregation. TPO modulates platelet activation possibly through protein-tyrosine-phosphorylation.

引用

页码：48 / 52

页数：5

共 30 条

[1] IDENTIFICATION AND CLONING OF A MEGAKARYOCYTE GROWTH AND DEVELOPMENT FACTOR THAT IS A LIGAND FOR THE CYTOKINE RECEPTOR MPL [J].

BARTLEY, TD ;

BOGENBERGER, J ;

HUNT, P ;

LI, YS ;

LU, HS ;

MARTIN, F ;

CHANG, MS ;

SAMAL, B ;

NICHOL, JL ;

SWIFT, S ;

JOHNSON, MJ ;

HSU, RY ;

PARKER, VP ;

SUGGS, S ;

SKRINE, JD ;

MEREWETHER, LA ;

CLOGSTON, C ;

HSU, E ;

HOKOM, MM ;

HORNKOHL, A ;

CHOI, E ;

PANGELINAN, M ;

SUN, Y ;

MAR, V ;

MCNINCH, J ;

SIMONET, L ;

JACOBSEN, F ;

XIE, C ;

SHUTTER, J ;

CHUTE, H ;

BASU, R ;

SELANDER, L ;

TROLLINGER, D ;

SIEU, L ;

PADILLA, D ;

TRAIL, G ;

ELLIOTT, G ;

IZUMI, R ;

COVEY, T ;

CROUSE, J ;

GARCIA, A ;

XU, W ;

DELCASTILLO, J ;

BIRON, J ;

COLE, S ;

HU, MCT ;

PACIFICI, R ;

PONTING, I ;

SARIS, C ;

WEN, D .

CELL, 1994, 77 (07) :1117-1124

[2] PDGF MODIFIES PHOSPHOINOSITIDE METABOLISM AND INHIBITS AGGREGATION AND RELEASE IN HUMAN-PLATELETS [J].

BRYCKAERT, MC ;

RENDU, F ;

TOBELEM, G ;

CAEN, J .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1986, 135 (01) :52-57

[3] JAK-STAT PATHWAYS AND TRANSCRIPTIONAL ACTIVATION IN RESPONSE TO IFNS AND OTHER EXTRACELLULAR SIGNALING PROTEINS [J].

DARNELL, JE ;

KERR, IM ;

STARK, GR .

SCIENCE, 1994, 264 (5164) :1415-1421

[4] THE MPI RECEPTOR IS EXPRESSED IN THE MEGAKARYOCYTIC LINEAGE FROM LATE PROGENITORS TO PLATELETS [J].

DEBILI, N ;

WENDLING, F ;

COSMAN, D ;

TITEUX, M ;

FLORINDO, C ;

DUSANTERFOURT, I ;

SCHOOLEY, K ;

METHIA, N ;

CHARON, M ;

NADOR, R ;

BETTAIEB, A ;

VAINCHENKER, W .

BLOOD, 1995, 85 (02) :391-401

[5] STIMULATION OF MEGAKARYOCYTOPOIESIS AND THROMBOPOIESIS BY THE C-MPL LIGAND [J].

DESAUVAGE, FJ ;

HASS, PE ;

SPENCER, SD ;

MALLOY, BE ;

GURNEY, AL ;

SPENCER, SA ;

DARBONNE, WC ;

HENZEL, WJ ;

WONG, SC ;

KUANG, WJ ;

OLES, KJ ;

HULTGREN, B ;

SOLBERG, LA ;

GOEDDEL, DV ;

EATON, DL .

NATURE, 1994, 369 (6481) :533-538

[6] THE C-MPL LIGAND (THROMBOPOIETIN) STIMULATES TYROSINE PHOSPHORYLATION OF JAK2, SHC, AND C-MPL [J].

DRACHMAN, JG ;

GRIFFIN, JD ;

KAUSHANSKY, K .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (10) :4979-4982

[7] DIFFERENTIAL REGULATION OF PROTEIN-TYROSINE PHOSPHATASES BY INTEGRIN ALPHA(IIB)BETA(3) THROUGH CYTOSKELETAL REORGANIZATION AND TYROSINE PHOSPHORYLATION IN HUMAN PLATELETS [J].

EZUMI, Y ;

TAKAYAMA, H ;

OKUMA, M .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (20) :11927-11934

[8]

GORDON MS, 1992, BLOOD, V80, P302

[9]

GRABAREK J, 1994, J BIOL CHEM, V269, P21718

[10] DISTINCT REGIONS OF C-MPL CYTOPLASMIC DOMAIN ARE COUPLED TO THE JAK-STAT SIGNAL-TRANSDUCTION PATHWAY AND SHC PHOSPHORYLATION [J].

GURNEY, AL ;

WONG, SC ;

HENZEL, WJ ;

DESAUVAGE, FJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (12) :5292-5296

← 1 2 3 →