Ligand

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Ligand
Receptor
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Receptor/Ligand Binds to promoter elements in DNA
and regulates transcription
Cortisol Receptor is located in the cytosol
Retinoid Receptors are in the nucleus
Target gene in the nucleus
Nucleus
Promoter
Regulation of Transcription
Primary and Secondary Responses
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Promoter
Promoter
Activation of transcription
Inhibition of transcription
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cAMP
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Some G protein linked receptors linked to Gq
activate Ca2 signaling
PIP2 plays an important role in Ca2 signaling
PIP2
PI
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Cleavage of PIP2 gives rise to Ca influx
Gq
(PLC b)
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Calmodulin is a Ca2 receptor that mediates many
Calcium responses
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CAM Kinases mediate most Ca2 responses
CAM Kinase II
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cAMP phosphodiesterase and adenylyl cyclase are
regulated by CAM Kinases
PKA Ca channels
Some CAM Kinases are PKA targets
CAM Kinases and PKA common targets
Regulation of Phosphorylase Kinase by cAMP and
Ca
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Ligand binding usually causes dimerization of the
receptor
EGF
EGF
outside of the cell
Membrane
inside of the cell
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P-Tyr binds downstream regulators containing SH2
domains
SH2 Domain
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Ras superfamily of small GTPases help relay
signals from RTKs
Stimulus
Downstream Signaling Pathways
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Mammalian Ras activation
SH2 Domain
(DRK)
SOS
Ras
GTP
Downstream pathways
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MAP Kinase Pathways can be mediated by members
of the Ras superfamily
Stimulus
Usually Ras superfamily
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Ca2 signaling can be activated by RTKs via PLC g
Ca2 signaling
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Cleavage of PIP2 gives rise to Ca influx
RTK
PLCg
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RTKs can activate PI3-Kinase
Other signaling pathways Cell survival
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PI3 Kinase (PI3K)
PI(3)P
PhosphatidylInositol(PI)
PI(3,4,5)P2
PI(3,4)P2
PI3K
PI3K PI4K
PI5K
Cell Survival Pathways Other Signaling Pathways
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PI3 Kinase (PI3K) and cell survival pathways
PI(3)P
PhosphatidylInositol(PI)
PI(3,4,5)P2
PI(3,4)P2
PI3K
PI3K PI4K
PI5K
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PI3K - AKT - Cell Survival
AKT
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Tyrosine Kinase (TK) Associated Receptors
LIGAND
outside of the cell
Membrane
inside of the cell
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Src binds to receptors with and without Tyr
Kinase activity
Schwartzberg (1998) 17 1463
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Src
Cell proliferation, Gene expression,
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receptors
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