Activation of phosphorylation of plasma membrane insulin-like growth factor-i receptors in the kidney of syrian hamsters by diethylstilbestrol Article

Chen, CW, Roy, D. (1995). Activation of phosphorylation of plasma membrane insulin-like growth factor-i receptors in the kidney of syrian hamsters by diethylstilbestrol . 16(6), 1339-1344. 10.1093/carcin/16.6.1339

cited authors

  • Chen, CW; Roy, D

fiu authors

abstract

  • In the present work we have investigated activation of phosphorylation of plasma membrane insulin-like growth factor-I receptors (IGF-IR) by diethylstilbestrol (DES). Insulin-like growth factor-I (IGF-I) stimulated the activity of membrane protein tyrosine kinasefs) (PTK) in both normal and DES-treated hamster kidneys. The level of IGF-I-stimulated PTK(s) almost doubled after 15 days of DES treatment Autophosphorylation experiments revealed that phosphorylation of a 95 kDa band (presumably the β subunit of IGF-IR) was 2-fold higher in the membranes of kidney from DES-treated animals compared with controls. To understand the mechanism of activation of IGF-I-dependent PTK by DES, we investigated the relationship between the binding capacity of IGF-I to membrane proteins and the level of IGF-IR. The binding of [125I]IGF-I to membranes from the DES-treated group was 30% higher than that of age-matched normal kidney (P < 0.001). Scatchard analysis of the binding data for both normal and DES-treated hamster kidney revealed a single class binding site for IGF-I with a dissociation constant (Kd) of 4.1 and 4.6 nM and a maximum binding capacity (Bmax of 1786 and 2086 fmol/200 μg protein respectively. Therefore, the difference observed in [125I]IGF-I binding between DES-treated and normal kidney membranes may be partially due to an increase in the number of IGF-I binding sites, with no change in the affinity of the receptors for IGF-I. An enhanced level of IGF-IRs in membranes from DES-treated animals was visualized by autoradiography following affinity labeling of membrane proteins subjected to SDS-PAGE. Under reducing conditions a molecular band of 132 kDa was evident The 132 kDa band represents the α-subunit of IGF-IRs. Northern blot analyses revealed that DES treatment increased the level of IGF-IR mRNA 2-fold compared with that of controls. These findings suggest that an enhanced level of IGF-IR coupled with qualitative changes may be responsible for the activation of IGF-I-dependent PTK on DES exposure. Whether the stimulation of IGF-IR phosphorylation by exposure to a carcinogenic dose of DES may be a factor in the induction of renal cancer in Syrian hamsters is not clear. © 1995 Oxford University Press.

publication date

  • June 1, 1995

Digital Object Identifier (DOI)

start page

  • 1339

end page

  • 1344

volume

  • 16

issue

  • 6