2010 Bio 317 Lecture 23

2010 Bio 317 Lecture 23 - 11/29/10 Addi$onal Receptor...

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Unformatted text preview: 11/29/10 Addi$onal Receptor Signaling Pathways Receptor Tyrosine Kinase Family 1 11/29/10 Figure 15-68 Molecular Biology of the Cell ( Garland Science 2008) Table 15-6 Molecular Biology of the Cell ( Garland Science 2008) 2 11/29/10 serine/threonine kinase receptors At the cell surface, the ligand binds a complex of transmembrane receptor serine/threonine kinases (types I and II) and induces transphosphoryla$on of the GS segments (red) in the type I receptor by the type II receptor kinases. The consequently ac$vated type I receptors phosphorylate selected Smads at C-terminal serines, and these receptor-ac$vated Smads (R-Smads) then form a complex with a common Smad4. Ac$vated Smad complexes translocate into the nucleus, where they regulate transcrip$on of target genes, through physical interac$on and func$onal coopera$on with DNA-binding transcrip$on factors (X) and CBP or p300 coac$vators. Ac$va$on of R-Smads by type I receptor kinases is inhibited by Smad6 or Smad7. R-Smads and Smad4 shuTle between nucleus and cytoplasm. Signaling and Gene Expression 3 11/29/10 4 11/29/10 5 11/29/10 6 11/29/10 7 11/29/10 CRE - cAMP Response Element Richard Goodman Gail Mandel Marc Montminy 8 11/29/10 CRE - cAMP Response Element CREB-binding site Eight bp palindrome: TGACGTCA (e.g. Somatosta$n gene) Usually within 100bp of TATA-box Less ac$ve if further upstream 400-350BC 9 11/29/10 CREB on CRE Alpha-helix Leucine Zipper MG 2+ ATenua$on Due to S/T Phosphatase PP-1 Passive Diffusion 10 11/29/10 P300 & CBP - Increase of Gene Expression 1. Histone acetyltransferase Acetylates lysine residues 2. Bind factors involved in cell growth and differen$a$on 3. Recruitment of basal transcrip$on machinery (RNA Pol-II) 11 11/29/10 Figure 15-60 Molecular Biology of the Cell ( Garland Science 2008) MAPK rsk 12 11/29/10 13 ...
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