Activation of Erk1/2 phosphorylation but not of Akt/Pkb through an inducible CSF1R/IRR-receptor construct in INS-1E β-cells

Abstract

Context: The insulin receptor-related receptor (IRR) is an orphan receptor belonging to the insulin receptor (IR) family. Despite its unknown function, the specific tissue expression and the high sequence homology with the IR and the insulin-like growth factor 1 receptor (IGF1R) suggest a biological role in β-cells.

Objectives: In this study we investigated the influence of a stimulatable IRR-tyrosine kinase on major IR/IGF1R signaling pathways and on proliferation and apoptosis of INS-1E β-cells.

Methods: INS-1E cells were stably transfected with a colony stimulating factor 1 receptor (CSF1R)/IRR construct activated by a macrophage colony stimulating factor.

Results and conclusion: After stimulation the construct showed time and dose dependent autophosphorylation and transient extracellular signal regulated kinase 1/2 activation. Protein kinase b was not phosphorylated and also an effect on proliferation and apoptosis of INS-1E could not be demonstrated. Thus, no obvious biologic function of the IRR is present in INS-1E β-cells.

Keywords::

• Insulin receptor-related receptor
• insulin-like growth factor 1 receptor
• pancreatic β-cells
• apoptosis
• signal transduction

Acknowledgements

This work was supported by grants from the German Research Council (Deutsche Forschungsgemeinschaft) KFO 152 ‘Atherobesity’ TP 5 and PF 225/3-1 as well as unrestricted grants from Ipsen, Merck Serono, Novo Nordisk, Pfizer and Sandoz to W.K., and a grant from the German Diabetes Society (Deutsche Diabetes Gesellschaft) to A.G.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.