Insulin modulates PC-1 processing and recruitment in cultured human cells

C. Menzaghi, R. Di Paola, G. Baj, A. Funaro, A. Arnulfo, T. Ercolino, N. Surico, F. Malavasi, V. Trischitta

Research output: Contribution to journalArticle

Abstract

We evaluated whether insulin signaling modulates plasma cell glycoprotein (PC-1) plasma membrane recruitment, posttranslational processing, and gene expression in human cultured cell lines. Insulin induced a fourfold increase (P <0.01) of membrane PC-1 expression by rapid and sensitive mechanism(s). This effect was reduced (P <0.05-0.01) by inhibition of phosphatidyl-inositol 3-kinase (200 nmol/l wortmannin) and S6 kinase (50 nmol/l rapamycin) activities and intracellular trafficking (50 μmol/l monensin) and was not accompanied by PC-1 gene expression changes. Moreover, at Western blot, insulin elicited the appearance, in both plasma membrane and cytosol, of a PC-1-related 146-kDa band (in addition to bands of 163, 117, 106, and 97 kDa observed also in absence of insulin) that was sensitive to endoglycosidase H. Finally, inhibition of PC-1 translocation to plasma membrane, by wortmannin pretreatment, increases insulin-stimulated receptor autophosphorylation. Our data indicate that insulin stimulates PC-1 posttranslational processing and translocation to the plasma membrane, which in turn impairs insulin receptor signaling. Bidirectional cross talk between insulin and PC-1, therefore, takes place, which may be part of the hormone self-desensitization mechanism.

Original languageEnglish
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume284
Issue number3 47-3
Publication statusPublished - Mar 1 2003

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Cultured Cells
Cells
Insulin
Processing
Cell Membrane
Cell membranes
Insulin Receptor
Gene expression
Ribosomal Protein S6 Kinases
Gene Expression
Monensin
Glycoside Hydrolases
Sirolimus
Phosphatidylinositols
Plasma Cells
Cytosol
Phosphotransferases
Western Blotting
Hormones
Cell Line

Keywords

  • Growth factor and ectoenzyme
  • Insulin desensitization
  • Insulin receptor
  • Insulin resistance
  • Plasma cell glycoprotein-1

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

Cite this

Insulin modulates PC-1 processing and recruitment in cultured human cells. / Menzaghi, C.; Di Paola, R.; Baj, G.; Funaro, A.; Arnulfo, A.; Ercolino, T.; Surico, N.; Malavasi, F.; Trischitta, V.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 284, No. 3 47-3, 01.03.2003.

Research output: Contribution to journalArticle

Menzaghi, C. ; Di Paola, R. ; Baj, G. ; Funaro, A. ; Arnulfo, A. ; Ercolino, T. ; Surico, N. ; Malavasi, F. ; Trischitta, V. / Insulin modulates PC-1 processing and recruitment in cultured human cells. In: American Journal of Physiology - Endocrinology and Metabolism. 2003 ; Vol. 284, No. 3 47-3.
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