Peer-Reviewed Journal Details
Mandatory Fields
O'Connor, R.,Fennelly, C.,Krause, D.;
Biochemical Society Transactions
Regulation of survival signals from the insulin-like growth factor-I receptor
Optional Fields
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.
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Grant Details