Lecture 13 - Lecture13 00:20 Slide2 geneexpression Slide3...

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Lecture 13 00:20 Slide 2 The ultimate outcome of most of these signaling pathways is going to change  gene expression. Slide 3 Slow response changes gene expression. Slide 4 Small hydrophobic signaling molecules, such as hormones and NO, doesn’t need  a transmembrane receptor to cross the plasma membrane.  Slide 5 Acetylcholine is an important signaling molecule in many different cell types. The  same receptor in muscle cell and salivary gland cell give you different results in  the cell. How does that happen? It happens because of all those complicated  downstream events. Similarly, this acetylcholine has other receptors. Because it’s  a different receptor, it interacts with a totally different signaling transduction  cascade and the molecular effect of acetylcholine binding in skeletal muscle cells  could be completely different.   Slide 6 When talking about signal transduction, think of kinases. Kinases add  phosphates to proteins and phosphatases remove phosphates from proteins.  Slide 7
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There are hundreds of kinases in your genome. Kinase domain in  serine/threonine kinases is very conserved, but the accessory sequences are all  unique to every individual kinase. That’s where the specificity for the participation  of each of these individual proteins in their pathways come from. cAMP- dependent kinase, PKA, interacts with cAMP and that’s what activates the  kinase. So that’s why PKA only phosphorylates proteins in the present of PKA,  whereas PKG phosphorylates proteins in the present of cGMP and that’s  because the accessory sequences are different. Tyrosine kinases are essentially  the same; you have a kinase domain that is slightly different than the  serine/threonine kinase domain, recognizable as a class in itself and these  kinases have unique accessory domain that gives each individual kinase a  specific property that allow them to be useful in individual signaling pathway.  Slide 8 Same is true for the phosphatases. It’s the accessory sequences and the other  proteins that interact with the phosphatases that actually mediate what proteins  they’re de-phosphorylating. Slide 9 Cells die when they don’t receive signals. Slide 12 Here’s one particular hormone receptor that is found in the cytoplasm associated  with HSP90 complex. The binding of the hormone releases this particular  receptor from this complex. It allows the hormone receptor to dimerize and this  dimer translocates to the nucleus, where these receptors have a DNA binding  domain that recognizes a specific sequence and they can have specific effects  on transcription.
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