RT Journal Article
SR Electronic
T1 Involvement of Protein Kinase C-ε in Signal Transduction of Thrombopoietin in Enhancement of Interleukin-3-Dependent Proliferation of Primitive Hematopoietic Progenitors
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 868
OP 875
VO 297
IS 3
A1 Noriyuki Shiroshita
A1 Manabu Musashi
A1 Keisuke Sakurada
A1 Kazuhiro Kimura
A1 Yuzo Tsuda
A1 Shuichi Ota
A1 Hiroshi Iwasaki
A1 Tamotsu Miyazaki
A1 Takashi Kato
A1 Hiroshi Miyazaki
A1 Akihiro Shimosaka
A1 Masahiro Asaka
YR 2001
UL http://jpet.aspetjournals.org/content/297/3/868.abstract
AB We studied the effect of thrombopoietin (TPO) on interleukin-3 (IL-3)-dependent bone marrow cell colony formation of mice to clarify the role of protein kinase C (PKC) in the signal transduction of TPO for the proliferation of primitive hematopoietic progenitors. TPO alone hardly yielded colonies. However, TPO in combination with IL-3 increased colony numbers synergistically from 2- to 4-fold, compared with those supported by IL-3 alone. Serial observation of colony development showed that TPO may hasten the appearance of colonies by shortening the dormant period (G0) of primitive progenitors. Immunocytochemical studies on PKC isoforms in progenitor cells stimulated with TPO have revealed that the expression pattern of PKC-ε is changed, but not that of PKC-α, -β, -γ, -δ, or -ζ. Selective PKC inhibitors, such as calphostin C and GF 109203X, and PKC-ε-specific translocation inhibitor peptide abrogated the enhancing effect of TPO on IL-3-dependent colony formation and the changes in the intracellular expression pattern of PKC-ε. These data taken together suggest that TPO has a direct effect on primitive progenitors and enhances IL-3-dependent colony formation, at least partly through the activation of PKC-ε. The American Society for Pharmacology and Experimental Therapeutics