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 language | English |
|---|---|
| Journal | American Journal of Physiology - Endocrinology and Metabolism |
| Volume | 284 |
| Issue number | 3 47-3 |
| Publication status | Published - Mar 1 2003 |
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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 journal › Article
}
TY - JOUR
T1 - Insulin modulates PC-1 processing and recruitment in cultured human cells
AU - Menzaghi, C.
AU - Di Paola, R.
AU - Baj, G.
AU - Funaro, A.
AU - Arnulfo, A.
AU - Ercolino, T.
AU - Surico, N.
AU - Malavasi, F.
AU - Trischitta, V.
PY - 2003/3/1
Y1 - 2003/3/1
N2 - 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.
AB - 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.
KW - Growth factor and ectoenzyme
KW - Insulin desensitization
KW - Insulin receptor
KW - Insulin resistance
KW - Plasma cell glycoprotein-1
UR - http://www.scopus.com/inward/record.url?scp=0037370739&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037370739&partnerID=8YFLogxK
M3 - Article
C2 - 12441313
AN - SCOPUS:0037370739
VL - 284
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6119
IS - 3 47-3
ER -