Involvement of protein kinase C-ε in signal transduction of thrombopoietin in enhancement of interleukin-3-dependent proliferation of primitive hematopoietic progenitors

Noriyuki Shiroshita, Manabu Musashi, Keisuke Sakurada, Kazuhiro Kimura, Yuzo Tsuda, Shuichi Ota, Hiroshi Iwasaki, Tamotsu Miyazaki, Takashi Kato, Hiroshi Miyazaki, Akihiro Shimosaka, Masahiro Asaka

研究成果: Article

8 引用 (Scopus)

抄録

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 (Go) 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.

元の言語English
ページ(範囲)868-875
ページ数8
ジャーナルJournal of Pharmacology and Experimental Therapeutics
297
発行部数3
出版物ステータスPublished - 2001 6
外部発表Yes

Fingerprint

Thrombopoietin
Interleukin-3
Protein Kinase C
Signal Transduction
Protein C Inhibitor
Protein Kinase Inhibitors
Bone Marrow Cells
Protein Isoforms
Stem Cells
Observation
Peptides

ASJC Scopus subject areas

  • Pharmacology

これを引用

Involvement of protein kinase C-ε in signal transduction of thrombopoietin in enhancement of interleukin-3-dependent proliferation of primitive hematopoietic progenitors. / Shiroshita, Noriyuki; Musashi, Manabu; Sakurada, Keisuke; Kimura, Kazuhiro; Tsuda, Yuzo; Ota, Shuichi; Iwasaki, Hiroshi; Miyazaki, Tamotsu; Kato, Takashi; Miyazaki, Hiroshi; Shimosaka, Akihiro; Asaka, Masahiro.

:: Journal of Pharmacology and Experimental Therapeutics, 巻 297, 番号 3, 06.2001, p. 868-875.

研究成果: Article

Shiroshita, N, Musashi, M, Sakurada, K, Kimura, K, Tsuda, Y, Ota, S, Iwasaki, H, Miyazaki, T, Kato, T, Miyazaki, H, Shimosaka, A & Asaka, M 2001, 'Involvement of protein kinase C-ε in signal transduction of thrombopoietin in enhancement of interleukin-3-dependent proliferation of primitive hematopoietic progenitors', Journal of Pharmacology and Experimental Therapeutics, 巻. 297, 番号 3, pp. 868-875.
Shiroshita, Noriyuki ; Musashi, Manabu ; Sakurada, Keisuke ; Kimura, Kazuhiro ; Tsuda, Yuzo ; Ota, Shuichi ; Iwasaki, Hiroshi ; Miyazaki, Tamotsu ; Kato, Takashi ; Miyazaki, Hiroshi ; Shimosaka, Akihiro ; Asaka, Masahiro. / Involvement of protein kinase C-ε in signal transduction of thrombopoietin in enhancement of interleukin-3-dependent proliferation of primitive hematopoietic progenitors. :: Journal of Pharmacology and Experimental Therapeutics. 2001 ; 巻 297, 番号 3. pp. 868-875.
@article{1f68c95b2a404365ac3c191f1bde1844,
title = "Involvement of protein kinase C-ε in signal transduction of thrombopoietin in enhancement of interleukin-3-dependent proliferation of primitive hematopoietic progenitors",
abstract = "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 (Go) 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.",
author = "Noriyuki Shiroshita and Manabu Musashi and Keisuke Sakurada and Kazuhiro Kimura and Yuzo Tsuda and Shuichi Ota and Hiroshi Iwasaki and Tamotsu Miyazaki and Takashi Kato and Hiroshi Miyazaki and Akihiro Shimosaka and Masahiro Asaka",
year = "2001",
month = "6",
language = "English",
volume = "297",
pages = "868--875",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "3",

}

TY - JOUR

T1 - Involvement of protein kinase C-ε in signal transduction of thrombopoietin in enhancement of interleukin-3-dependent proliferation of primitive hematopoietic progenitors

AU - Shiroshita, Noriyuki

AU - Musashi, Manabu

AU - Sakurada, Keisuke

AU - Kimura, Kazuhiro

AU - Tsuda, Yuzo

AU - Ota, Shuichi

AU - Iwasaki, Hiroshi

AU - Miyazaki, Tamotsu

AU - Kato, Takashi

AU - Miyazaki, Hiroshi

AU - Shimosaka, Akihiro

AU - Asaka, Masahiro

PY - 2001/6

Y1 - 2001/6

N2 - 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 (Go) 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.

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 (Go) 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.

UR - http://www.scopus.com/inward/record.url?scp=0034996035&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034996035&partnerID=8YFLogxK

M3 - Article

C2 - 11356906

AN - SCOPUS:0034996035

VL - 297

SP - 868

EP - 875

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 3

ER -