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By Derek LeRoith

ISBN-10: 0306478463

ISBN-13: 9780306478468

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90 The importance of Phe701 was reinforced in the studies of hIR- or hIGF-IR-based chimeric minireceptors. 91 Sequence comparisons of hIRR, hIR and hIGF-IR suggest the substitution of Thr for Phe at the position equivalent to 701 in IGF-IR is responsible for this loss of ligand binding by the chimeras containing the carboxy-terminal peptide from the hIRR α-chain. IGF Mutations IGF-I and -II contain two extra regions compared to insulin; the C region between the B and A domains and the D region at the C-terminus (Fig.

These phosphotyrosine containing motifs are binding sites for adaptor and effector molecules in receptor signaling pathways. Binding of the adaptor protein Shc and the large docking protein IRS-1 to receptor phosphotyrosine 950 results in activation of MAP kinase and PI3 kinase/Akt , major signaling pathways of the IGF1R. Other IGF1R binding partners have been described which include Grb10, Crk-II, CSK, 14-3-3 proteins, p85 and p55γ regulatory subunits of PI3-K, SHP-2, SH2-B, Gαi, JAKs, and SOCS proteins.

Luo RZT, Beniac DR, Fernandes A et al. Quaternary structure of the insulin-insulin receptor complex. Science 1999; 285:1077-1080. 75. Ottensmeyer FP, Beniac DR, Luo RZT et al. Mechanism of transmembrane signaling: Insulin binding and the insulin receptor. Biochemistry 2000; 39:12103-12112. 76. Ottensmeyer FP, Beniac DR, Luo RZT et al. Mechanism of transmembrane signaling: Insulin binding and the insulin receptor—Correction. Biochemistry 2001; 40:6988-6988. 77. Christiansen K, Tranum-Jensen J, Carlsen J et al.

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