Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences

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Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences 1. Cyclic AMP signalling pathway. 2. Cyclic ADP-ribose (cADPR) signalling and nicotinic acid–adenine dinucleotide phosphate (NAADP) signalling 3. Voltage-operated channels (VOCs) 4. Receptor-operated channels (ROCs) 5. Stimuli that activate phospholipase C (PLC( 6. PtdIns 3-kinase signalling 7. Nitric oxide (NO)/cyclic GMP signalling 8. Redox signalling. Many receptors act through NADPH oxidase (NOX 9. Mitogen-activated protein kinase (MAPK) 10. Nuclear factor κB(NF-κB) signalling. 11. Phospholipase D (PLD) signalling. 12. Sphingomyelin signalling pathway 13. Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signalling. 14. Smad signalling pathway 15. Wnt signalling pathways. 16. Hedgehog signalling pathway 17. Hippo signalling pathway 18. Notch signalling pathway. 19. Endoplasmic reticulum (ER) stress signalling.Theendoplasmic reticulum (ER) stress signalling pathway 20. AMP signalling pathway.. These receptors then transfer information across the membrane using a variety of transducers and ampliﬁers that engage a diverse repertoire of intracellular signalling pathways (Pathways 1--16 in Module 2: Figure cell signalling pathways). The phosphoinositide signalling and Ca 2 + signalling systems (Pathways 2--6) have been grouped together because they contain a number of related signalling pathways that often interact with each other. The other categories are the pathways that are activated by signals generated fromwithin the cell (Pathways 17 and 18). There are a number of metabolic messengers that act from within the cell to initiate a variety of signalling pathways. GTP-binding proteins often play a central role in the transduction process responsible for initiating many of these signalling pathways Not included in Module 2: Figure cell signalling pathways are some additional signalling pathways that have speciﬁc functions in regulating various aspects of cell metabolism, such as sterol sensing and cholesterol biosynthesis, that control the level of cholesterol in cell membranes. Another example is found in the NAD signalling pathways, where NAD functions to regulate a number of cellular processes, including energy metabolism, gene transcription, DNA repair and perhaps ageing as well Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Cyclic AMP signalling pathway Usually depends upon the activation of G-protein-coupled receptors (GPCRs) Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

adenylyl cyclase structure Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Regulatory properties and distribution of adenylyl cyclase. Modiﬁed from Table I in Whorton and Sunahara 2003. Reproduced from Handbook of Cell Signaling, Volume 2 (edited by R.A. Bradshaw and E.A. Dennis), Whorton, M.R. and Sunahara, R.K., Adenylyl cyclases, pp. 419--426. Copyright (2003), with permission from Elsevier. Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Organization and function of the cyclic AMP signalling pathway Rac is inactive when bound to GDP, but switches into an active form when this GDP is exchanged for GTP. This GTP for GDP exchange is facilitated by a number of guanine nucleotide exchange factors (GEFs) such as Tiam, Kalirin, Vav, SoS and P-Rex, which are sensitive to various messengers such as Ca 2 + , PtdIns3,4,5P 3 (PIP )orGßγ subunits of heterotrimeric G proteins. The activated Rac/GTP then relays information out to different signalling pathways as described in the text. Further details concerning the role of Wiskott--Aldrich syndrome protein (WASP) verprolin homologous (WAVE ) Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Function of the Rho monomeric G protein in cell signal transduction. Rho is a typical Gprotein that is activated when GDP is exchanged for GTP. This exchange is facilitated by a number of Rho guanine nucleotide exchange factors (RhoGEFs). For example, the ephexins mediate the action of protein tyrosine-linked receptors (PTKRs), such as the ephrin receptors, whereas the G protein-coupled receptors (GPCRs) use the a subunit of heterotrimeric G proteins to activate leukaemia-associated RhoGEF (LARG), p115-RhoGEF or PDZ-RhoGEF. The activated Rho/GTP complex then activates a number of signalling systems as outlined in the text. Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Function of the Cdc42 monomeric G protein in signal transduction When bound to GDP, Cdc42 is inactive, but it is activated when the GDP is exchanged for GTP. This exchange is accelerated by guanine nucleotide exchange factors (GEFs), but how these are activated is still somewhat of a mystery. The primary action of the Cdc42/GTP complex is to stimulate actin assembly by inhibiting the action of coﬁlin, by promoting actin polymerization by acting on actin/proﬁlin and Wiskott--Aldrich syndrome protein (WASP) Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Function of the Arf monomeric G-protein in signal transduction When bound to GDP, Arf is inactive, but it is activated when the GDP is exchanged for GTP. This exchange is accelerated by guanine nucleotide- exchange factors (GEFs), but how these are activated is still somewhat of a mystery. In some cases, such as Golgi-speciﬁc brefeldin A resistant factor 1 (GBF1), activation depends on other G-proteins such as Rab1 (Module 4: Figure COPI-coated vesicles). The primary action of the Arfs is to stimulate actin polymerization and membrane remodelling during protein trafﬁcking Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Summary of the monomeric G proteins with their guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department

Peyman Keyhanvar, MD, PhD, MBA, Iran University of Medical Sciences Faculty of Advanced Technologies in Medicine, Nanobiomedicine Department