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Type: Journal article
Title: Molecular mechanisms underlying insulin-like growth factor action: How mutations in the GH: IGF axis lead to short stature
Author: Forbes, B.
Citation: Pediatric Endocrinology Reviews, 2011; 8(4):374-381
Publisher: YS Medical Media Ltd
Issue Date: 2011
ISSN: 1565-4753
Statement of
B. E. Forbes
Abstract: Insulin-like growth factors (IGFs) act via the Type 1 IGF receptor (IGF-1R) to promote growth and development. Recent structural and site-directed mutagenesis studies have provided detailed insight into the mechanism of interaction between the IGFs and the IGF-IR. Studies of the insulin: insulin receptor interaction have provided important additional understanding of the mechanisms underlying the IGF:IGF-1R interaction. The recent crystal structure of the insulin receptor ectodomain showed a folded over conformation accommodating two potential ligand binding pockets. The ligand interacts with the receptor at two different sites within a binding pocket to achieve high affinity binding and activation of the receptor. In this review the effect of mutations in the human IGF1 and IGF-1R genes so for reported are explained in terms of the effect on ligand binding and receptor activation. The severity of patient phenotype can generally be correlated to the effect of the mutation on protein structure and function.
Keywords: Humans
Growth Disorders
Human Growth Hormone
Receptor, IGF Type 1
Insulin-Like Growth Factor I
Insulin-Like Growth Factor II
Receptor, IGF Type 2
Body Height
Amino Acid Sequence
Protein Structure, Tertiary
Structure-Activity Relationship
Molecular Sequence Data
Rights: Copyright status unknown
Appears in Collections:Aurora harvest 5
Molecular and Biomedical Science publications

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