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Lecture 11

BIO120H1 Lecture Notes - Lecture 11: Creb-Binding Protein, Response Element, Protein A


Department
Biology
Course Code
BIO120H1
Professor
Darrel Desveaux
Lecture
11

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- *SURWHLQ.and subunits anchored in the lipid bilayer, inactive form bound to
GDP, activated receptor induces conformational change in trimeric protein and
GDP exchanged for GTP, GTP concentration in cytosol naturally high, .and -
units dissociate
BIO241 Lecture 11 Cell Communication II
- .VXEXQLWWDUJHWDdenylyl cyclase, one .VXEXQLW activates one adenylyl cyclase
which produces many cAMP which activates PKA (usually inactive in the cell)
o PKA made of two types of subunits: 2 catalytic: carry out P-ation and 2
regulatory: keep catalytic units in inactive form
o catalytic subunits P-ate specific substrate proteins
o cAMP binds to regulatory subunits Æ conformational change in
regulatory subunits that dissociate with catalytic subunits, activating them
o PKA effects are transient, phosphatases deP-ate target proteins
o e.g. glycogen: adrenalin (ligand), produced in adrenal gland as a stress
response Æ to promote glucose release to provide energy, will activate
PKA via G proteins
Promote breakdown off glycogen
Inhibit glycogen synthesis
o Glycogen is broken down into glucose-1-P Æ glucose-6-P via glycolytic
pathway and is trapped in the cell
o PKA P-ates glycogen phosphorylase kinase which P-ates glycogen
phosphorylase which acts to break glycogen down, PKA also P-ates to
inhibit glycogen synthase (which acts to synthesize glycogen)
o Rapid response, immediate effect but can be slow in different cell types
because of transcription factors
cAMP responsive elements
(CRE) in DNA is bound by
CREB (binding protein)
transcription factor
activated PKA will enter
nucleus to P-ate/activate
CREB which recruits CBP
(coactivator) Æ transcription
of target genes in the liver,
e.g. glucose-6-phosphatase
which deP-ates glucose-6-P
to glucose so that it can be
released from the liver into the blood (slow process)
- Enzyme-linked cell surface receptors
o Membrane spanning proteins, extracellular ligand-binding domain,
intracellular domain has enzyme activity, e.g. kinase domains
o Receptors inactive state is monomeric, ligand binding Æ dimerization of
receptors and activates catalytic/kinase domain or recruits and activates
associated enzyme to receptor
o Receptor tyrosine kinases (RTK): ligands (growth factors, hormones) pro-
life signals, responses (cell proliferation, differentiation, survival)
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