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


OBJECTIVE
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 beta-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.


CONCLUSIONS
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 beta-cells.
Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany.
Rico
R
Vogel
Antje
A
Garten
Jürgen
J
Klammt
Anja
A
Barnikol-Oettler
Wieland
W
Kiess
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D011972:Receptor, Insulin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013002:Somatomedins / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D007328:Insulin; D013002:Somatomedins; D014443:Tyrosine; D016173:Macrophage Colony-Stimulating Factor; D011972:Receptor, Insulin; D016186:Receptor, Macrophage Colony-Stimulating Factor; C066542:insulin receptor-related receptor; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3