Involvement of protein kinase C-epsilon in signal transduction of thrombopoietin in enhancement of interleukin-3-dependent proliferation of primitivehematopoietic progenitors

Citation
N. Shiroshita et al., Involvement of protein kinase C-epsilon in signal transduction of thrombopoietin in enhancement of interleukin-3-dependent proliferation of primitivehematopoietic progenitors, J PHARM EXP, 297(3), 2001, pp. 868-875
Citations number
39
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
ISSN journal
0022-3565 → ACNP
Volume
297
Issue
3
Year of publication
2001
Pages
868 - 875
Database
ISI
SICI code
0022-3565(200106)297:3<868:IOPKCI>2.0.ZU;2-Q
Abstract
We studied the effect of thrombopoietin (TPO) on interleukin-3 (IL-3)-depen dent bone marrow cell colony formation of mice to clarify the role of prote in kinase C (PKC) in the signal transduction of TPO for the proliferation o f primitive hematopoietic progenitors. TPO alone hardly yielded colonies. H owever, TPO in combination with IL-3 increased colony numbers synergistical ly from 2- to 4-fold, compared with those supported by IL-3 alone. Serial o bservation of colony development showed that TPO may hasten the appearance of colonies by shortening the dormant period (G(o)) of primitive progenitor s. Immunocytochemical studies on PKC isoforms in progenitor cells stimulate d with TPO have revealed that the expression pattern of PKC-epsilon is chan ged, but not that of PKC-alpha, -beta, -gamma, -delta, or -xi. Selective PK C inhibitors, such as calphostin C and GF 109203X, and PKC-epsilon -specifi c translocation inhibitor peptide abrogated the enhancing effect of TPO on IL-3-dependent colony formation and the changes in the intracellular expres sion pattern of PKC-epsilon. These data taken together suggest that TPO has a direct effect on primitive progenitors and enhances IL-3-dependent colon y formation, at least partly through the activation of PKC-epsilon.