1. Lecture 07 – Second MessengersI Lecture 07 – Second MessengersI BIOL 5190/6190 Cellular & Molecular Singal Transduction Prepared by Bob Locy Last modified -13F

2. Cell Signalling Mechanisms Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 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.

3. Extracellular receptors 1.G-protein-coupled receptors 2.Tyrosine and histidine kinase-type receptors 3.Integrin receptors 4.Toll gate receptors 5.Ligand-gated ion channels Intracellular receptors 1.Steroid hormone receptors 2.Lipophyllic receptors (vitamins eg.)

4. CSB Fig 02:01 Cell signalling pathways CSB Fig 02:01 Cell signalling pathways Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012

5. Transducers Second Messengers I 1.Cyclic AMP signaling 1.Calcium second messengers 2.Lipophillic second messengers

6. Evaluation only. Created with Aspose.PowerPoint. Copyright 2004 Aspose Pty Ltd. CSB Fig 2:02 Adenylyl cyclase structure CSB Fig 2:02 Adenylyl cyclase structure Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012

7. CSB Fig 2:03 Cyclic AMP signalling CSB Fig 2:03 Cyclic AMP signalling Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012

8. CSB Fig 2:04 Protein kinase A (PKA) CSB Fig 2:04 Protein kinase A (PKA)

9. CSB Fig 2:03 Cyclic AMP signalling CSB Fig 2:03 Cyclic AMP signalling Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012

10. CSB Fig 2:05 G protein binary switching CSB Fig 2:05 G protein binary switching

11. Module 2:Table heterotrimeric G proteins The 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 protein Function G protein α (Gα) subunits GαsStimulate adenylyl cyclase Gαolf Stimulate 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) GαqStimulate 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 )

12. Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 CSB Fig 2:06 Heterotrimeric G protein signalling CSB Fig 2:06 Heterotrimeric G protein signalling

13. Monomeric G-proteins Family of 150 proteins Ras is founding member Subfamilies (refer to table in Module 2, CSB) Ras family – ca 36 members Rho family – ca 22 members Rac family – ca 4 members Rab family – > 50 members Arf Family - numerous

14. Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 CSB Fig 2:07 Ras signalling CSB Fig 2:07 Ras signalling

15. Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 CSB Fig 2:08 Rab signalling CSB Fig 2:08 Rab signalling

16. Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 CSB Fig 2:09 Rac signalling CSB Fig 2:09 Rac signalling

17. Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 CSB Fig 2:10 Rho signalling CSB Fig 2:10 Rho signalling

18. Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 CSB Fig 2:11 Cdc42 signalling CSB Fig 2:11 Cdc42 signalling

19. Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 CSB Fig 2:12 Arf signalling CSB Fig 2:12 Arf signalling

20. Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 CSB Fig 2:13 Rho-regulated kinases CSB Fig 2:13 Rho-regulated kinases