MessengersI BIOL 51906190 Cellular amp Molecular Singal Transduction Prepared by Bob Locy Last modified 13F Cell Signalling Mechanisms Cell Signalling Biology Michael J ID: 341307
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Slide1
Lecture 07 – Second MessengersI
BIOL 5190/6190 Cellular & Molecular
Singal
Transduction
Prepared by Bob Locy
Last modified -13FSlide2
Cell
Signalling
Mechanisms
Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012
Typical, molecular signaling pathways are initiated via receptors which perceive the presence of the activating signal.
The signal passes through a series of intracellular transducers and second messengers which may or may not lead to an amplification of the signal.
Ultimately second messenger sensors are activated, modulate of effector molecules which lead cellular responses.
The complexity of cellular signaling results from the “cross-talk” between multiple signaling pathways, and among the specific intracellular aspects of the pathways within each cell type.Slide3
Extracellular receptorsG-protein-coupled receptorsTyrosine and histidine kinase-type receptorsIntegrin receptorsToll gate receptors
Ligand
-gated ion channels
Intracellular receptorsSteroid hormone receptors
Lipophyllic receptors (vitamins eg.)Slide4
CSB Fig 02:01 Cell
signalling
pathways
Cell
Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 Slide5
Transducers Second Messengers ICyclic AMP signaling
Calcium
second messengers
Lipophillic second messengers Slide6
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CSB Fig 2:02 Adenylyl
cyclase structure Cell Signalling Biology - Michael J.
Berridge
- www.cellsignallingbiology.org - 2012 Slide7
CSB Fig 2:03 Cyclic AMP
signalling
Cell
Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 Slide8
Cell
Signalling
Biology - Michael J.
Berridge - www.cellsignallingbiology.org - 2012
CSB Fig 2:04 Protein kinase A (PKA) Slide9
CSB Fig 2:03 Cyclic AMP
signalling
Cell
Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 Slide10
Cell
Signalling
Biology - Michael J.
Berridge - www.cellsignallingbiology.org - 2012
CSB Fig 2:05 G protein binary switching Slide11
Module 2:Table heterotrimeric G proteinsThe heterotrimeric
proteins are assembled from subunits taken from the G protein
α
(Gα), G protein β (Gβ) and G protein γ (Gγ) families.Heterotrimeric G proteinFunctionG protein α
(Gα) subunits GαsStimulate adenylyl cyclase GαolfStimulate adenylyl cyclase Gαi1
Inhibit adenylyl cyclase
Gαi2
Inhibit adenylyl cyclase
Gαi3
Inhibit adenylyl cyclase
Gαo1
Inhibit adenylyl cyclase
Gαo2
Inhibit
adenylyl
cyclase
Gαt1
Stimulate
cGMP
phosphodiesterase
in rod photoreceptors
Gαt2
Stimulate
cGMP
phosphodiesterase
in rod photoreceptors
Gz
Close K+ channels. Inhibits
exocytosis
Gαgust
Stimulate
phospholipase
Cβ (PLCβ) (see Module 10: Figure taste receptor cells and Module 7: Figure L cells)
Gαq
Stimulate
phospholipase
Cβ (PLCβ)
Gα11
Stimulate
phospholipase
Cβ (PLCβ)
Gα14
Stimulate phospholipase Cβ (PLCβ)
Gα15
Stimulate phospholipase Cβ (PLCβ)
Gα16
Stimulate phospholipase Cβ (PLCβ)
Gα12
Stimulate
RhoGEFs
to activate
Rho
Gα13
Stimulate
RhoGEFs
to activate
Rho
G protein
β
(Gβ) subunits; β1–β5
These
β
subunits combine with
γ
subunits to form
βγ
dimers
that have a number of control functions (for details see Module 2: Figure
heterotrimeric
G protein
signalling
)
G protein
γ
(Gγ) subunits; γ1–γ11
These
γ
subunits combine with
β
subunits to form
βγ
dimers
that have a number of control functions (for details see Module 2: Figure
heterotrimeric
G protein
signalling
)Slide12
Cell
Signalling
Biology - Michael J.
Berridge - www.cellsignallingbiology.org - 2012
CSB Fig 2:06 Heterotrimeric G protein signalling Slide13
Monomeric G-proteinsFamily of 150 proteinsRas is founding memberSubfamilies (refer to table in Module 2, CSB)Ras family – ca 36 membersRho family – ca 22 membersRac family – ca 4 membersRab family – > 50 members
Arf
Family - numerousSlide14
Cell
Signalling
Biology - Michael J.
Berridge - www.cellsignallingbiology.org - 2012
CSB Fig 2:07 Ras signalling Slide15
Cell
Signalling
Biology - Michael J.
Berridge - www.cellsignallingbiology.org - 2012
CSB Fig 2:08 Rab signalling Slide16
Cell
Signalling
Biology - Michael J.
Berridge - www.cellsignallingbiology.org - 2012
CSB Fig 2:09 Rac signalling Slide17
Cell
Signalling
Biology - Michael J.
Berridge - www.cellsignallingbiology.org - 2012
CSB Fig 2:10 Rho signalling Slide18
Cell
Signalling
Biology - Michael J.
Berridge - www.cellsignallingbiology.org - 2012
CSB Fig 2:11 Cdc42 signalling Slide19
Cell
Signalling
Biology - Michael J.
Berridge - www.cellsignallingbiology.org - 2012
CSB Fig 2:12 Arf signalling Slide20
Cell
Signalling
Biology - Michael J.
Berridge - www.cellsignallingbiology.org - 2012
CSB Fig 2:13 Rho-regulated kinases