Exam 3 Review - Exam 3 Review Signaling Over Time and Space o Some genes are induced faster than others during transcription o Sustained signaling

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Exam 3 Review: Signaling Over Time and Space: o Some genes are induced faster than others during transcription. o Sustained signaling is what causes NGF to cause the neuronal phenotype while EGF only causes transient signaling. This is because ERK/MapK translocates from the cytoplasm into the nucleus after 15-20 minutes of sustained signaling only. If a receptor (EGF included) is overexpressed it will give rise to sustained signaling because it cannot be degraded fast enough. o Elimination of a number of EGFRs on a cell surface is normal to regulate the pathway, and NGFRs are degraded about 4 times slower, allowing for sustained signaling. EGFRs are endocytosed by Clathrin, a cage-like structural protein. Endosomal signaling continues until EGFR degredation (Ligand-Receptor complex is internalized) NGF endosomes last for a much longer time and do not use the clathrin pathway Rap is a protein localized for endosomes!! o NGF is a target-derived growth factor (It is produced by target cells) o Internalized receptors travel up retrograde transport machinery, utilizing microtubules to get to the cell body for degredation. o Experimental Example: There is a subset of receptors that are spatially located near the Q-dot, showing that they have been retrogradedly transported into the cell-body. o By the time normal EGFR gets to the cell body it is lysosomal and cannot signal. KSR is a cell-surface anchoring protein that binds Raf, MEK, and ERK together at the cell membrane. MP1 and p14 are endosomal scaffolding proteins that bind MEK and Erk together at the endosome. AKAP localizes kinases with specific substrates. o Binds PKA to a phosphodiesterase, lowering cAMP levels. o Also binds PKC, PKD, etc. . Signaling Crosstalk:
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o PLC β is activated by G-Proteins while PLC ϒ is activated through growth factor pathways. o Ca 2+ can activate RasGEF and Ad Cyclase. o PKA phosphorylates Tyrosine Hydroxylase at serine 40, while ERK does it at serine 31, and CamK II does it at serine 19. Phosphorylation releases inhibition of regulatory domain on catalytic domain, and maximal activation occurs when it is phosphorylated in all three places. Signaling networks are analyzed from various viewpoints: o View from a particular input and analyzing the entire network as a standalone system o View from interactions between similarly acting inputs o View from a particular signaling component and combining mini-networks of components. o View of the entire system. Early Signaling events in the establishment of Axon/Dendrite Polarity o New cells are born at the ventricular zone of the developing brain and migrate to different regions. The trailing process becomes the axon. o
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This note was uploaded on 12/13/2011 for the course BIO 362 taught by Professor Walikarzai during the Spring '10 term at SUNY Stony Brook.

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Exam 3 Review - Exam 3 Review Signaling Over Time and Space o Some genes are induced faster than others during transcription o Sustained signaling

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