Regulation of survival signals from the insulin-like growth factor-I receptor.
Suppression of apoptosis by survival factors is important for the maintenance of normal tissue homoeostasis and the response to infection or injury. Survival factors such as insulin-like growth factor-I (IGF-I) initiate a signalling cascade that starts by tyrosine phosphorylation of substrates leading to the activation of serine kinases that modulate the activity of members of the Bcl-2 family, which regulates the apoptotic machinery in most cells. Tumour cells often have enhanced survival mechanisms due either to up-regulation of the IGF-I receptor and its ligands or to loss of function of a phosphatase (PTEN) that regulates part of this survival pathway. The C-terminus of the IGF-I receptor appears to be a regulatory domain for the anti-apoptotic activity of this receptor, and certain residues within the C-terminus are essential for this regulatory activity. Knowledge of the proteins and pathways, which interact with these C-terminal domains, should lead us to ways of modulating IGF-I-mediated survival in tumours.
O'Connor
R
R
Department of Biochemistry, University College Cork, Lee Maltings, Ireland.
Fennelly
C
C
Krause
D
D
D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans; D002470:Cell Survival; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D008954:Models, Biological; D016296:Mutagenesis; D017434:Protein Structure, Tertiary; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1