Regulation of insulin-like growth factor-1 receptor expression and signaling

Sammanfattning: Insulin-like growth factor-1 receptor (IGF-1R), a member of the insulin receptor tyrosine kinase family is a broadly expressed transmembrane receptor that plays a key role in malignant cell growth. IGF-1R transmits information provided by extracellular stimuli into intracellular signaling pathways resulting in the subsequent regulation of various effector systems. Under normal cellular conditions IGF-1R signaling network is tightly regulated. The most prominent regulator of IGF-1R signal termination is desensitization of receptors by the removal of activated receptors from the cell surface mediated by accelerated endocytosis. For some membrane receptors the signal mediating receptor internalization/downregulation is constituted by ubiquitination. Recently, we showed that IGF-1R undergoes ubiquitination following ligand stimulation. The proto-oncogene MDM2 was identified as an E3 ligase involved in IGF-1R ubiquitination. Studies on new events involved in IGF-1R downregulation and intracellular signaling constitute the subject of the present thesis.