Abstract
To investigate the molecular mechanisms mediating hematopoietic cell differentiation and mitogenesis by activation of the platelet-derived growth factor β receptor (PDGF-βR), the wild type PDGF-βR (PDGF-βRWT) and tyrosine to phenylalanine mutants of the PDGF-βR, including F751, F966, F970, F1009, F1021 and F1009/F1021 were overexpressed in FDC-P2 myeloid progenitor cells by retroviral-mediated gene transfer. Stimulation of PDGF-βRWT and F966, F970 and F1009 infectants with PDGF-BB led to the increased expression of monocytic differentiation markers. In contrast, activation of PDGF-βR in the parental line or the F1021 or F1009/F1021 mutant infectants failed to induce monocytic differentiation. PDGF-BB stimulation of PDGF-βRWT, F751, F966, F970 and F1009 infectants led to pronounced DNA synthesis, whereas F1021 and F1009/F1021 infectants did not reveal any increase in mitogenesis when compared to that of the FDC-P2 line. While PDGF stimulation of FDC-P2 cells overexpressing PDGF-βRWT led to a pronounced increase in inositol phosphate formation due to phospholipase C-γ (PLC-γ) activation, PDGF-BB induced phosphoinositol hydrolysis was completely abolished in the F1021 and F1009/F1021 infectants. GF 109203X, a specific inhibitor of protein kinase C (PKC) activation, fully blocked PDGF-βR-mediated monocytic differentiation and mitogenesis. Taken together, these results suggest that stimulation of the PDGF-βR signaling pathway can mediate monocytic differentiation when PDGF-βR is expressed at sufficient levels and that activation of PLC-γ and PKC plays a pivotal role in PDGF-βR-mediated differentiation and mitogenesis in FDC-P2 cell system.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Alimandi, M., Heidaran, M., Gutkind, J. et al. PLC-γ activation is required for PDGF-βR-mediated mitogenesis and monocytic differentiation of myeloid progenitor cells. Oncogene 15, 585–593 (1997). https://doi.org/10.1038/sj.onc.1201221
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1201221
Keywords
This article is cited by
-
Protein kinase C (PKC) as a drug target in chronic lymphocytic leukemia
Medical Oncology (2013)
-
Tyrosine kinase oncogenes in normal hematopoiesis and hematological disease
Oncogene (2002)
-
Growth factor signaling pathways in vascular development
Oncogene (1999)
-
APS, an adaptor protein containing PH and SH2 domains, is associated with the PDGF receptor and c-Cbl and inhibits PDGF-induced mitogenesis
Oncogene (1999)