The effect of staurosporine, a protein kinase inhibitor, on asialoglycoprotein receptor endocytosis

Robert Fallon, Maria Danaher

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Receptor-mediated endocytosis via coated pits is modulated by the activity of protein kinases and protein phosphorylation. We examined the effects of the potent protein kinase inhibitor staurosporine (SSP) on endocytosis of the asialoglycoprotein (ASGP) receptor in HepG2 cells. Staurosporine caused a rapid ( 1 2 = 8 min). This resulted in increased ASGP receptors at the plasma membrane (140% of control) while the total number of receptors per cell was unchanged. Receptor up-regulation was half-maximal at 30 nM SSP. At this concentration staurosporine also inhibited the internalization of iodinated transferrin by HepG2 cells and SK Hep-1 cells, another human hepatoma-derived cell line. Staurosporine was without effect on the non-receptor-mediated uptake of Lucifer yellow by pinocytosis. We investigated the possible involvement of protein kinase C in the inhibitory effects of staurosporine on receptor endocytosis. The active protein kinase C inhibitor H7 did not inhibit ASGP receptor internalization. Furthermore depletion of cellular protein kinase C by overnight incubation with 1 μM phorbol myristate acetate did not abrogate the SSP effect. Together these data suggest that the mechanism of SSP action is independent of the inhibition of protein kinase C. In conclusion staurosporine is a potent and rapid inhibitor of receptor trafficking which is specific for receptor internalization from the plasma membrane.

Original languageEnglish (US)
Pages (from-to)420-426
Number of pages7
JournalExperimental Cell Research
Volume203
Issue number2
DOIs
StatePublished - 1992
Externally publishedYes

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Asialoglycoprotein Receptor
Staurosporine
Protein Kinase Inhibitors
Endocytosis
Protein Kinase C
Hep G2 Cells
Cell Membrane
Pinocytosis
Protein C Inhibitor
Tetradecanoylphorbol Acetate
Transferrin
Protein Kinases
Hepatocellular Carcinoma
Up-Regulation
Phosphorylation

ASJC Scopus subject areas

  • Cell Biology

Cite this

The effect of staurosporine, a protein kinase inhibitor, on asialoglycoprotein receptor endocytosis. / Fallon, Robert; Danaher, Maria.

In: Experimental Cell Research, Vol. 203, No. 2, 1992, p. 420-426.

Research output: Contribution to journalArticle

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