Specificity in ligand binding and intracellular signalling by insulin and insulin-like growth factor receptors.

Abstract:

:The physiological roles of insulin and insulin-like growth factors (IGFs) are distinct, with insulin acting to regulate cellular uptake and metabolism of fuels, whereas IGFs promote cell growth, survival and differentiation. The only components of signalling pathways known to be unique to insulin and IGFs are their respective receptors, and even these display substantial structural and functional similarity. Specificity of action in vivo must in part reflect relative levels of receptor expression in different tissues. The extent to which the receptors differ in intrinsic signalling capacity remains unclear, but specificity might in principle arise from differences in ligand-binding mechanism or properties of intracellular domains. To identify ligand binding determinants we expressed receptor fragments as soluble proteins. Both N-terminal domains and a C-terminal peptide sequence from the alpha-subunit are essential for ligand binding with moderate affinity. However, binding of ligand with high affinity and specificity requires higher-order structure. To compare signalling capacities, we constructed chimaeras containing intracellular domains of insulin or IGF receptors fused to the extracellular portion of TrkC. Expression and activation of these chimaeras in cell lines reveals subtle differences in signalling and end-point responses, which may depend on cell background.

journal_name

Biochem Soc Trans

authors

Siddle K,Ursø B,Niesler CA,Cope DL,Molina L,Surinya KH,Soos MA

doi

10.1042/bst0290513

keywords:

subject

Has Abstract

pub_date

2001-08-01 00:00:00

pages

513-25

issue

Pt 4

eissn

0300-5127

issn

1470-8752

journal_volume

29

pub_type

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