Biol300%20Lecture%2010%20SH-1

Biol300%20Lecture%2010%20SH-1 - complex and recruit a...

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Lecture 9 Enzyme-linked receptors: Receptor serine/threonine kinases; Intracellular receptors Reading for Lecture 9: Lodish Ch. 15, pp. 656-657; Ch. 16 pp. 665-672
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Homo- or heterodimer
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1) A type III (RIII), a proteoglycan, concentrates ligand at the cell surface. 2) When ligand binds always active RII, RII recruits and phosphorylates RI. 3) RI then phosphorylates an R-Smad. 4) Phosphorylation of R-Smad exposes its NLS. 5) Two phosphorylated molecules of the R-Smad interact with a co-Smad and with importin- β . 6) The entire complex translocates into the nucleus. 7) In the nucleus RAN-GTP causes dissociation of Imp- β 8) A nuclear transcription factor (here TFE3) associates with the complex. 9) The complex binds to regulatory sequences in a precise geometry to regulate transcription.
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Inhibition of pathway: by inhibitory (I)-Smads that bind activated RI and prevent binding of R-Smads
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Inhibition (2): by proteins that bind DNA-bound R-Smad/Co-Smad
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Unformatted text preview: complex and recruit a histone deacetylase Usually, cells have to respond to a combination of signals 16_39_integrate_signal.jpg Integration of signals/cross-regulation Signal integration/cross-regulation or inhibited Smad1 Which signal transduction cascade phosphorylates Smad1? EGF increases basal level of Smad1 phosphorylation PI3K inhibitor Phosphorylation is gone in Smad1 mutant and with a MAPKK (MEK) inhibitor Which kinase of MAPK cascade phosphorylates Smad1? Activated type I Receptor and [ 32 P]ATP causes phosphorylation of wt and mutant Smad1 In vitro kinase assay with recombinant purified proteins: Activated Erk (MAPK) and [ 32 P]ATP can only phosphorylate wt Smad1 What is the consequence of EGF-induced Smad1 phosphorylation? R-Smad/Co-Smad complexes can still form But R-Smad/Co-Smad complex can no longer go to nucleus Smad1 antibody staining TGF-...
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This note was uploaded on 10/12/2011 for the course BIOL 300 taught by Professor Nilson during the Spring '11 term at McGill.

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Biol300%20Lecture%2010%20SH-1 - complex and recruit a...

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