Stimulation of the platelet-derived growth factor β receptor signaling pathway activates protein kinase C-δ

Weiqun Li, Jin Chen Yu, Paolo Michieli, John F. Beeler, Nelson Ellmore, Mohammad A. Heidaran, Jacalyn H. Pierce

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Abstract

The murine myeloid progenitor cell line 32D was recently shown to undergo monocytic differentiation when protein kinase C-δ (PKC-δ) was overexpressed and activated by 12-O-tetradecanoylphorbol-13-acetate (TPA) (H. Mischak, J. H. Pierce, J. Goodnight, M. G. Kazanietz, P. M. Blumberg, and J. F. Mushinski, J. Biol. Chem. 268:20110-20115, 1993). Tyrosine phosphorylation of PKC-δ occurred when PKC-δ-transfected 32D cells were stimulated by TPA (W. Li, H. Mischak, J.-C. Yu, L.-M. Wang, J. F. Mushinski, M. A. Heidaran, and J. H. Pierce, J. Biol. Chem. 269:2349-2352, 1994). In order to elucidate the role played by PKC-δ in response to activation of a receptor tyrosine kinase, we transfected platelet-derived growth factor β receptor (PDGF-βR) alone (32D/PDGF-βR) or together with PKC-δ (32D/PDGF-βR/PKC-δ) into 32D cells. NIH 3T3 cells which endogenously express both PDGF-αR and PDGF-βR were also transfected with PKC-δ (NIH 3T3/PKC-δ). Like TPA treatment, PDGF- BB stimulation caused striking phosphorylation of PKC-δ in vivo and translocation of some PKC-δ from the cytosol fraction to the membrane fraction in both cell systems. Some of the phosphorylation induced by PDGF- BB treatment was found to be on a tyrosine residue(s). Tyrosine- phosphorylated PKC-δ was observed only for the membrane fraction after stimulation with PDGF-BB or TPA. The enzymatic activity of PKC-δ in the membrane fraction also increased after stimulation with TPA or PDGF, providing a positive correlation between PKC-δ tyrosine phosphorylation and its activation. Overnight treatment of 32D/PDGF-βR/PKC-δ cells with PDGF- BB induced monocytic differentiation as judged by an increase in expression of cell surface macrophage differentiation markers. PDGF-BB had much weaker effects on 32D/PDGF-βR cell differentiation, suggesting that increased PKC- δ expression enhanced monocytic differentiation. These results indicate that PKC-δ is a downstream molecule in the PDGFR signaling pathway and may play a pivotal role in PDGF-βR-mediated cell differentiation.

Original languageEnglish
Pages (from-to)6727-6735
Number of pages9
JournalMolecular and Cellular Biology
Volume14
Issue number10
Publication statusPublished - Oct 1994

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Platelet-Derived Growth Factor Receptors
Protein Kinase C
Tetradecanoylphorbol Acetate
Phosphorylation
Protein-Tyrosine Kinases
Membranes
Tyrosine
Cell Differentiation
Myeloid Progenitor Cells
NIH 3T3 Cells
Differentiation Antigens

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

Cite this

Li, W., Yu, J. C., Michieli, P., Beeler, J. F., Ellmore, N., Heidaran, M. A., & Pierce, J. H. (1994). Stimulation of the platelet-derived growth factor β receptor signaling pathway activates protein kinase C-δ. Molecular and Cellular Biology, 14(10), 6727-6735.

Stimulation of the platelet-derived growth factor β receptor signaling pathway activates protein kinase C-δ. / Li, Weiqun; Yu, Jin Chen; Michieli, Paolo; Beeler, John F.; Ellmore, Nelson; Heidaran, Mohammad A.; Pierce, Jacalyn H.

In: Molecular and Cellular Biology, Vol. 14, No. 10, 10.1994, p. 6727-6735.

Research output: Contribution to journalArticle

Li, W, Yu, JC, Michieli, P, Beeler, JF, Ellmore, N, Heidaran, MA & Pierce, JH 1994, 'Stimulation of the platelet-derived growth factor β receptor signaling pathway activates protein kinase C-δ', Molecular and Cellular Biology, vol. 14, no. 10, pp. 6727-6735.
Li, Weiqun ; Yu, Jin Chen ; Michieli, Paolo ; Beeler, John F. ; Ellmore, Nelson ; Heidaran, Mohammad A. ; Pierce, Jacalyn H. / Stimulation of the platelet-derived growth factor β receptor signaling pathway activates protein kinase C-δ. In: Molecular and Cellular Biology. 1994 ; Vol. 14, No. 10. pp. 6727-6735.
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abstract = "The murine myeloid progenitor cell line 32D was recently shown to undergo monocytic differentiation when protein kinase C-δ (PKC-δ) was overexpressed and activated by 12-O-tetradecanoylphorbol-13-acetate (TPA) (H. Mischak, J. H. Pierce, J. Goodnight, M. G. Kazanietz, P. M. Blumberg, and J. F. Mushinski, J. Biol. Chem. 268:20110-20115, 1993). Tyrosine phosphorylation of PKC-δ occurred when PKC-δ-transfected 32D cells were stimulated by TPA (W. Li, H. Mischak, J.-C. Yu, L.-M. Wang, J. F. Mushinski, M. A. Heidaran, and J. H. Pierce, J. Biol. Chem. 269:2349-2352, 1994). In order to elucidate the role played by PKC-δ in response to activation of a receptor tyrosine kinase, we transfected platelet-derived growth factor β receptor (PDGF-βR) alone (32D/PDGF-βR) or together with PKC-δ (32D/PDGF-βR/PKC-δ) into 32D cells. NIH 3T3 cells which endogenously express both PDGF-αR and PDGF-βR were also transfected with PKC-δ (NIH 3T3/PKC-δ). Like TPA treatment, PDGF- BB stimulation caused striking phosphorylation of PKC-δ in vivo and translocation of some PKC-δ from the cytosol fraction to the membrane fraction in both cell systems. Some of the phosphorylation induced by PDGF- BB treatment was found to be on a tyrosine residue(s). Tyrosine- phosphorylated PKC-δ was observed only for the membrane fraction after stimulation with PDGF-BB or TPA. The enzymatic activity of PKC-δ in the membrane fraction also increased after stimulation with TPA or PDGF, providing a positive correlation between PKC-δ tyrosine phosphorylation and its activation. Overnight treatment of 32D/PDGF-βR/PKC-δ cells with PDGF- BB induced monocytic differentiation as judged by an increase in expression of cell surface macrophage differentiation markers. PDGF-BB had much weaker effects on 32D/PDGF-βR cell differentiation, suggesting that increased PKC- δ expression enhanced monocytic differentiation. These results indicate that PKC-δ is a downstream molecule in the PDGFR signaling pathway and may play a pivotal role in PDGF-βR-mediated cell differentiation.",
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