BIO 1140 Lecture Notes - Lecture 13: Nuclear Membrane, Growth Factor, Phospholipid

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Mon, February 29 - Lecture 13 Signal transduction - intro transcription
Slide 3
How do you get Ras to turn on? It needs to change its conformation, binds to Sos in order to
change its affinity from GDP to GTP and change conformation. Sos is activated when it is bound
to GBR2 and the receptor. As is lipid-bound, so it can move within the membrane but cannot
travel directly to the receptor. Goal of the pathway is to get Ras activated so through a series of
phosphorylation, can initiate transcription.
Slide 3
PLCy can activate the receptor right away. Its an enzyme and a lipase- it cuts lipids. Its favourite
target it PIP2. PIP2 is a fatty acid anchored lipid, has a different polar head group. When PLCy
cleaves it, it leaves a fatty acid in the membrane? Calcium clearly doesn't always lead to
apoptosis inside a cell. Calcium also does a lot of positive things in the cell, as well as being
involved in programming cell death.
Slide 3
Activating PIP2 releases two secondary messengers. PLCy is an amplifier.
Slide 4
DAG isn't entirely a protein, but you can anchor something to it that makes it one. (not a GPI
anchored protein because those are on the outside of the membrane).
Slide 5
They have a ligand binding receptor outside the cell. When the cell changes conformation, it
recruits the trimeric G proteins. (Alpha, Beta, Gamma subunits). When they bind the G protein to
the receptor, induces the alpha subunit to exchange GDP for GTP etc.
Slide 6
2 main pathways to understand: cAMP and PIP (IP3)
Slide 8
cAMP pathway. Where is the amplification? The amount of cAMP produced by enzyme
(adenylate cyclase). Nothing really stopping the production of multiple alpha submits,. Most
likely more than only one adenylate cycles in the membrane. How do you shut PKA down?
Slide 8
Gi is an inhibiting protein. Ligand binds to G protein receptor, activates alpha subunit and goes
on to interact with amplifier enzyme (shutting it down), inhibiting adenylate cyclase and
therefore reducing the amount of cAMP available, allowing everything to return to the baseline
Slide 8
Regulatory subunit of PKA and Catalytic subunit of PKA must separate in order to activate, must
merge back together to deactivate.
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