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Thrombopoietin induces tyrosine phosphorylation and activation of the Janus
kinase, JAK2
PJ Tortolani, JA Johnston, CM Bacon, DW McVicar, A Shimosaka, D Linnekin, DL Longo and JJ O'Shea
Arthritis and Rheumatism Branch, National Institute of Arthritis and
Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda,
MD 20892-1820, USA.
Thrombopoietin (TPO) is a recently characterized growth and differentiation
factor for megakaryocytes and platelets that exerts its effects via the
receptor, c-MpI. This receptor is a member of the hematopoietin receptor
superfamily and is essential for megakaryocyte maturation; however, the
molecular mechanisms of TPO and c-MpI action have not been elucidated.
Recently, the Janus kinases have emerged as important elements in signaling
via this family of receptors. In this report, we show that, in the M07e
megakaryocytic cell line, which expresses c-MpI and proliferates in
response to TPO, TPO induces phosphorylation of a number of substrates
between 80 and 140 kD. Specifically, we show that stimulation with TPO
induces the rapid tyrosine phosphorylation of a 130-kD protein that we
identify as the Janus kinase, JAK2. However, no detectable tyrosine
phosphorylation of JAK1, JAK3, or TYK2 was observed. TPO also induced
activation of JAK2 phosphotransferase activity in vitro. Taken together,
these data indicate that JAK2 likely plays a key role in TPO-mediated
signal transduction.
Volume 85,
Issue 12,
pp. 3444-3451,
06/15/1995
Copyright © 1995 by The American Society of Hematology
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