Membrane Receptors

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Membrane Receptors and Signal Transduction
Cascades
(Stryer chapter 14, Lodish chapters 15.6, 15.7
16.2-4)
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Cell-surface receptors belong to different classes
(insulin, epidermal growth factor)
(smell, taste, vision, blood pressure etc.)
(IL2, 4 etc. as well as epo)
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G protein-coupled receptors contain 7
transmembrane alpha-helices
4
(No Transcript)
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Catalytic domains are brought together upon
activation
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Activation of adenylate cyclase increases
intracellular cAMP levels
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(triggers glycogen catabolism)
factor 104
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Second messengers amplify the initial stimulus
and Ca2
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PKA mediated activation of cAMP responsive genes
protein kinase A (cAMP dep. kinase)
HAT
target genes control metabolism, memory formation
cAMP response element
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GPCRs can also activate phospholipase C (instead
of adenylate cyclase) to generate IP3 and DAG
Transmembrane Protein channel (TRP) opens to
restore intracellular Ca2 in ER
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phospatidylinositol (PI) is a phospholipid in the
plasma membrane
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Activation of phospholipase C can also result in
signaling through PKG (dep. on cGMP)
nitroglycerin (given against intense chest pain
of angina) decomposes to NO
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Receptor tyrosine kinases (RTKs) dimerize upon
hormone binding
Insulin works through RTKs
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Epidermal growth factor receptor requires
an adaptor to activate the G protein Ras
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GRB2 G protein-signaling receptor binding
protein 2 Shc Src kinase homology complex
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Sos (guanine-nucleotide exchange factor)
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MAP kinase activation cascade controls cell
growth and proliferation
14-3-3 binds phosphorylated target proteins Raf
Ras activated factor MEK MAP and ERK activating
kinase
MAP Mitogen activating protein kinase
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Cytokine receptors induce JAK/STAT signaling
cascades and work independently of G proteins
bound by STATs
JAK janus kinase STAT signal transducers and
activators of transcription
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Erythropoietin stimulates the formation of red
blood cells in the bone marrow
low oxygen (sensed by kidney cells,
they monitor oxygen level) more Epo
more red blood cells (erys make usually
45-47 of all blood cells)
SH Src kinase homology
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Secreted decoy receptors bind hormone and
prevent receptor activation
OPG osteoprotegerindecoy that inhibits bone
resorption
Receptor activator for NF-kB
Osteoclasts bind to bone through podosomes and
form a tight seal upon interaction with
osteoblasts through RANKL/RANK. Osteoclasts are
responsible for bone resorption. They secrete
HCl and proteases (highly corrosive).
Osteoblasts suppress bone resorption by secreting
osteoprotegerin, which inhibits the direct
interaction with osteoclasts.
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What you need to know Different classes of cell
surface receptors 1) GPCRs (7 transmembrane recep
tors), 2) cytokine receptors and 3) RTKs (class 2
and 3 dimerize upon ligand binding work w/o 2nd
messengers). Signaling through second messengers
provides signal amplification 2nd messengers are
cAMP, cGMP, DAG, IP3 opens calcium channels, and
calcium. Role of 2nd messengers is to activate
kinases PKA (cAMP), PKC (Ca2 and DAG), PKG
(cGMP). PKs then activate transcription factors
by phosphorylation. RTKs, such as the EGF
receptor signal through G proteins that
induce the MAP kinase pathway (rasgtrafgtMEKgtMAP)
to activate transcription factors. Cytokine
receptors can activate transcription factors
independently of 2nd messengers and G proteins
through the JAK/ STAT pathway. What are decoy
receptors? (bind ligand w/o signaling compete
with their receptor counterpart for ligand
binding), one well-studied example is
osteoprotegerin, which inhibits bone resorption
by osteoclasts.