TY - JOUR
T1 - Thrombopoietin induces tyrosine phosphorylation and activation of the Janus kinase, JAK2
AU - Tortolani, P. Justin
AU - Johnston, James A.
AU - Bacon, Chris M.
AU - McVicar, Daniel W.
AU - Shimosaka, Akihiro
AU - Linnekin, Diana
AU - Longo, Dan L.
AU - O'Shea, John J.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1995/6/15
Y1 - 1995/6/15
N2 - 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.
AB - 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.
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U2 - 10.1182/blood.v85.12.3444.bloodjournal85123444
DO - 10.1182/blood.v85.12.3444.bloodjournal85123444
M3 - Article
C2 - 7780132
AN - SCOPUS:0029051429
SN - 0006-4971
VL - 85
SP - 3444
EP - 3451
JO - Blood
JF - Blood
IS - 12
ER -