Lecture 10 Signaling pt 2

Lecture 10 Signaling pt 2 - Biochemistry Chapter 14:...

Info iconThis preview shows pages 1–14. Sign up to view the full content.

View Full Document Right Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: Biochemistry Chapter 14: Signal-Transduction Pathways Copyright by W. H. Freeman and Company Berg Tymoczko Stryer Part II signal transduction pathways Stimulus Response Insulin signaling and phosphorylation cascades Receptors include protein kinases as part of their structures Binding of insulin results in the activation of kinase activity and phosphorylation The insulin receptor is a dimer Disulfide Bond Peptide hormone The insulin receptor is a receptor tyrosine kinase Phosphorylates tyrosine residues (not serine or threonine residues) The kinase is part of the receptor Insulin binding results in receptor phosphorylation and activation phosphorylation of the activation loop results in activation of the kinase activity of the receptor Hubbard (1999) Progress Biophys. Mcl Biol. 71, 343 hosphorylation induces changes in conformation of the activation loops of the IR ctivation loops atalytic loops eptide substrate ( pink ) ote: AMP-PNP in the IRK3P structure 8 8 Insulin signaling Phosphorylation of the cytoplasmic domain of the receptor creates binding sites for proteins: Insulin receptor substrate-1 (IRS-1) Modular structure of insulin receptor substrates PH domain : binds phosphoinositide lipids; functions to membrane localize IRS PTB domain : binds pY-965 in the juxtamembrane region of the IR YXXM sequences : sites phosphorylated by the IR; when phosphorylated, these sites are recognized by specific proteins with Src homology 2 (SH2) domains IRS proteins PH domain PTB domain YXXM sites IRS proteins are adaptor proteins : devoid of enzymatic activity phosphorylation by the IR creates binding sites for specific proteins that transmit signals downstream Insulin signaling Phosphorylation of IRS proteins creates a binding site for the lipid kinase, Phosphatidylinositide-3-kinase (PI3K) Phosphatidylinositide 3-kinase Phosphatidylinositide 3-kinase (PI3K) Converts PIP 2 into PIP 3 Two subunits: p85 regulatory subunit, and p110 catalytic subunit PI3K binds to IRS through its p85 regulatory subunit The SH2 domains of the regulatory subunit bind p-IRS proteins SH2 domain bound to a...
View Full Document

Page1 / 44

Lecture 10 Signaling pt 2 - Biochemistry Chapter 14:...

This preview shows document pages 1 - 14. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online