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

被引:11
作者
Menzaghi, C [1 ]
Di Paola, R
Baj, G
Funaro, A
Arnulfo, A
Ercolino, T
Surico, N
Malavasi, F
Trischitta, V
机构
[1] Sci Inst Casa Sollievo Sofferenza, Unit Endocrinol, I-71013 Foggia, Italy
[2] Univ Turin, Sch Med, Immunogenet Lab, Dept Genet Biol & Biochem, I-10126 Turin, Italy
[3] Ctr Med Expt, I-10126 Turin, Italy
[4] Univ A Avogadro Eastern Piedmont, Div Obstet & Gynecol, Dept Med Sci, I-28100 Novara, Italy
[5] Univ Roma La Sapienza, Dept Clin Sci, I-00161 Rome, Italy
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 2003年 / 284卷 / 03期
关键词
insulin receptor; insulin resistance; growth factor and ectoenzyme; insulin desensitization; plasma cell glycoprotein-1;
D O I
10.1152/ajpendo.00503.2001
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 phosphatidylinositol 3-kinase (200 nmol/l wortmannin) and S6 kinase (50 nmol/l rapamycin) activities and intracellular trafficking (50 mumol/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.
引用
收藏
页码:E514 / E520
页数:7
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