Role of a serine/threonine kinase, Mst1, in megakaryocyte differentiation.

Abstract:

:Platelets, which play a central role in thrombosis and hemostasis, develop from megakaryocytes. Signal transduction originated from the megakaryocyte growth and development factor, the Mpl ligand, which leads to megakaryocyte differentiation, polyploidization, and maturation, has been gradually characterized. In this study, we report the inducibility of Mst1, a recently described serine/threonine kinase, by Mpl ligand and the effect of its induced expression on megakaryocyte differentiation. The steady-state level of mst1 message and Mst1-associated kinase activity increased in response to Mpl ligand. Ectopic expression of human mst1 in a mouse megakaryocytic cell line resulted in a drastic increase in DNA content per cell. Elevated expression of megakaryocyte differentiation markers, such as acetylcholine esterase, PF4, and GPIIb was also observed in hmst1-expressing cells. Activation of p38 MAPK, a known downstream effector of Mst1, was shown to be required for polyploidization, but not for enhanced expression of differentiation markers. Our study thus designates Mst1 as a Mpl ligand-responsive signaling molecule that promotes induction of lineage-specific cellular programming.

journal_name

J Cell Biochem

authors

Sun S,Ravid K

doi

10.1002/(sici)1097-4644(20000101)76:1<44::aid-jcb6

subject

Has Abstract

pub_date

1999-11-01 00:00:00

pages

44-60

issue

1

eissn

0730-2312

issn

1097-4644

pii

10.1002/(SICI)1097-4644(20000101)76:1<44::AID-JCB6

journal_volume

76

pub_type

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