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PMID:1845984

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Citation

Bürgisser, DM, Roth, BV, Giger, R, Lüthi, C, Weigl, S, Zarn, J and Humbel, RE (1991) Mutants of human insulin-like growth factor II with altered affinities for the type 1 and type 2 insulin-like growth factor receptor. J. Biol. Chem. 266:1029-33

Abstract

With the aim to produce insulin-like growth factors (IGF) with enhanced specificity for the type 1 or type 2 IGF receptors, three mutants of IGF II have been prepared and expressed in NIH-3T3 cells. IGF II mutated at Tyr27 to Leu and Glu showed a 25- and 54-fold decrease in affinity for the type 1 IGF receptor and a 3.4- and 9.2-fold decrease in affinity for the type 2 IGF receptor. IGF II mutated at Phe48 to Glu showed a 18-fold decrease in affinity for the type 2 IGF receptor and a 2.8-fold decrease in affinity for the type 1 IGF receptor. These affinities were measured in radioreceptor assays using type 1 or 2 IGF receptor overexpressing cells. Data obtained on receptor cross-linking and thymidine incorporation assays confirmed the results of the radioreceptor assays. It is concluded that mutations of Tyr27 preferentially decrease binding to the type 1 IGF receptor and of Phe48 to the type 2 IGF receptor, either by the loss of a residue involved in receptor binding or by preferentially destabilizing the region involved in receptor binding.

Links

PubMed

Keywords

Amino Acid Sequence; Base Sequence; Blotting, Western; Cell Line; Cross-Linking Reagents; Electrophoresis, Polyacrylamide Gel; Humans; Insulin-Like Growth Factor II/genetics; Insulin-Like Growth Factor II/metabolism; Molecular Sequence Data; Mutation; Radioimmunoassay; Radioligand Assay; Receptors, Cell Surface/metabolism; Receptors, Somatomedin; Thymidine/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:IGF2

involved_in

GO:0008286: insulin receptor signaling pathway

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IGF2

enables

GO:0005159: insulin-like growth factor receptor binding

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete


See also

References

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