The recent discovery of thrombopoietin has enhanced our understanding of both hematopoiesis and platelet production. Thrombopoietin supports hematopoietic stem cell survival and expansion as well as promoting all aspects of megakaryocyte development. The hormone displays many structural similarities to other members of the hematopoietic cytokine family and some notable differences, and regulation of its expression requires both receptor-mediated removal and other mechanisms. Thrombopoietin induces receptor dimerization and tyrosine phosphorylation, and a series of signaling events including activation of JAK/STAT, Shc/Ras/MAPK and PI3K/Akt; these pathways overlap with those induced by other cytokines, but the differences that lead to the unique biological effects of the hormone are gradually being uncovered. Our growing appreciation of how cytokine signaling pathways are translated into megakaryocyte development is discussed. (C) 2002 Elsevier Science Ltd. All rights reserved.
机构:
NCI, FREDERICK CANC RES & DEV CTR, MACROMOLEC STRUCT LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USANCI, FREDERICK CANC RES & DEV CTR, MACROMOLEC STRUCT LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA
GUSTCHINA, A
;
ZDANOV, A
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NCI, FREDERICK CANC RES & DEV CTR, MACROMOLEC STRUCT LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USANCI, FREDERICK CANC RES & DEV CTR, MACROMOLEC STRUCT LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA
ZDANOV, A
;
SCHALKHIHI, C
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NCI, FREDERICK CANC RES & DEV CTR, MACROMOLEC STRUCT LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USANCI, FREDERICK CANC RES & DEV CTR, MACROMOLEC STRUCT LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA
SCHALKHIHI, C
;
WLODAWER, A
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NCI, FREDERICK CANC RES & DEV CTR, MACROMOLEC STRUCT LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USANCI, FREDERICK CANC RES & DEV CTR, MACROMOLEC STRUCT LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA
机构:
PO Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, AustraliaPO Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia
机构:
NCI, FREDERICK CANC RES & DEV CTR, MACROMOLEC STRUCT LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USANCI, FREDERICK CANC RES & DEV CTR, MACROMOLEC STRUCT LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA
GUSTCHINA, A
;
ZDANOV, A
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机构:
NCI, FREDERICK CANC RES & DEV CTR, MACROMOLEC STRUCT LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USANCI, FREDERICK CANC RES & DEV CTR, MACROMOLEC STRUCT LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA
ZDANOV, A
;
SCHALKHIHI, C
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机构:
NCI, FREDERICK CANC RES & DEV CTR, MACROMOLEC STRUCT LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USANCI, FREDERICK CANC RES & DEV CTR, MACROMOLEC STRUCT LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA
SCHALKHIHI, C
;
WLODAWER, A
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机构:
NCI, FREDERICK CANC RES & DEV CTR, MACROMOLEC STRUCT LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USANCI, FREDERICK CANC RES & DEV CTR, MACROMOLEC STRUCT LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA
机构:
PO Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, AustraliaPO Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia