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Chapter 9B: RTK Signaling - Coggle Diagram
Chapter 9B: RTK Signaling
Typical animal cell surface receptors
GPCR: Activation - conformational change
ligand-gated ion channel: activation - conformational change
receptor kinase: activation - dimerization activates enzyme activity
Activation of a GPCR by an extracellular ligand --> conformational change
G-proteins have 2 forms
ACTIVE: GTP bound (a separated from B/Y)
INACTIVE: GDP bound, stabilized trimer
active --> inactive bc of GTP HYDROLYSIS to GDP
inactive --> active (GPCR activation)
Pathway
adrenaline -->
receptor -->
activates G-protein +GTP (transducin) -->
activates adenylyl cyclase -->
activates cAMP -->
activates PKA
Review questions
Why does paracrine signaling not activate the cell that is producing the signaling molecule?
Cell doesn't have the proper receptor - the receptor doesn't bind that specific signaling molecule
You strip off all proteins on the cell surface. Now you add a specific signaling molecule and the cell still responds. Why
The receptor is in the INTERIOR of the cell
Receptor kinases are activated by "growth factors"
Activation: dimerization of 2 receptor kinases activates enzyme activity, phosphorylates by transferring a phosphate from ATP to another molecule
PATHWAY
ligand binds to 2 receptors at once (extracellular)
The 2 receptors dimerize
Kinase part of the receptor (intracellular) activates
each member of the receptor phosphorylates each other
addition of new phosphates = binding site for intracellular signaling molecules
activate these intracellular signaling proteins (i.e. RAS)
Growth factors give multicellular animal cells license to survive and grow
growth is REGULATED to maintain functional organs
cell growth, cell division, cell survival is dictated by signaling molecule
DIFFERENT FROM MICROORGANISMS: unruly cell growth and division "feast or famine"
discovery of growth factor PDGF - platelet derived growth factor
experiment: culture with serum (PDGF CONTAINS GROWTH FACTORS) vs. culture with plasma
mesenchymal cells (i.e. fibroblasts) require PDGF to grow and survive
Different cell types respond to different growth factors
RAS (an intracellular signaling molecule G-protein activated by activation of receptor kinase): A small GTPase
RAS-GDP = OFF
MAP kinase pathway
RAS-GTP = ON
MAPkinase cascade = ON
Outcome: proliferation = permission to divide
activation of MAP kinase pathway can license cell division
ex. Tumor cells (oncogenes)
cells secrete "own" growth factor (doesn't need permission from extracellular growth factor to divide)
have Receptor kinase that is always ON: HER2
Express version of RAS that can't shut itself off --> cell proliferation
Have another kinase ON all the time: BRAF
During transmission of signals inside cells, the signal is amplified and spread
takes a localized, weak incoming signal and generate a broad, strong response
Enzymes that contribute to amplification: adenylate cyclase, PKA
Signals are rapidly shut off again --> ready for next signal
When ligand unbinds
GPCR shutting on/off: G-proteins automatically shut off
PKA that turns off cAMP --> AMP
phosphatases remove phosphates