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Chapter 8 Signal Transduction Events
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a general process of signal transduction pathway
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Singnaling Molecules
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Receptors for Water-solulble Signaling Molecules Gated channels Gated channels Catalytic receptors Catalytic receptors Receptors coupled to G protein Receptors coupled to G protein
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Receptors for Lipid-soluble Singaling Molecules Steroid Hormones HAT : histone acetyltransferase
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(Histone transacetylase) (Histone deacetylase) Thyroid Hormones
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Catalytic Receptors/Tyrosine Kinases Catalytic Receptors/Tyrosine Kinases
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Organization of Receptor Protein- Tyrosine Kinases
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Structure of Protein Kinases cAMP-dependent protein kinases Ca 2+ -calmodulin-dependent protein kinases PDGF receptor kinases
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FGF Signal Transduction Pathway PKD : protein kinase D, PKC : protein kinase C, PDK : phosphoinositide-dependent kinase, DAG : diacylglycerol
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Activation of Ras following ligand binding to receptor tyrosine kinase (1) (growth factor receptor-bound protein 2) (Srk homology 2,3) (Epithermal growth factor) (Growth factor receptor-bound protein 2) (Son of sevenless)
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A signal transduction from Ras to MAP kinase (2) mitogen-activated or extracellular-signal-regulated protein kinase (MEK) mitogen-activated protein kinase (MAPK)
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Induction of gene transcription by activated MAP kinase (3) Transcription factor (TCF) Serum response factor (SRF) Serum responsive element (SRE)
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ErbB-induced Signaling Pathway
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JAK-STAT signaling pathway of cytokine receptors
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Pathways of MAP Kinase Activation in Mammalian Cells
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TGF- and TGF -like Ligands/Their Type I and II Receptors
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TGF- Receptor-mediated Signaling 6
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Two signalling pathways of the TGF- superfamil y
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Nodal-mediated Signaling for Determination of Left-right Asymmetry
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Wnt Signaling Pathway
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Hedgehog Cleavage and Singling Pathway
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Notch-mediated Signaling Pathway
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Signaling Network Model for Heart Valve Development
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Steroid Hormone-mediated Signaling Pathway
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(Histone transacetylase) (Histone deacetylase) Thyroid Hormone-mediated Signaling Pathway
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G Protein-Linked Receptors G Protein-Linked Receptors
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Structure of a G Protein-Coupled Receptor
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Operational Model of G Protein-coupled Receptors
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Synthesis and Degradation of cAMP
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Regulation of Protein Kinase A
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Regulation of Glycogen Metabolism by cAMP
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Amplification of an External Signal Downstream from a Cell-surface Receptor
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Activation and Inhibition of Adenylate Cyclase (Adnocorticotropic hormone)
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Operational Model of Muscarinic Acetylcholine Receptor
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Transducin (G t )-mediated signal transduction PDE: cGMP Phosphodiesterase
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Cyclic AMP-Inducible Gene Expression (cyclic AMP-response element binding protein)
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Renin-antiotensin-aldosterone System
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Ion Channel-linked Receptors Ion Channel-linked Receptors
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Structure of Representative Neurotransmitters (Na + influx) (Cl - influx)
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Architecture of Ligand-gated Receptors
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The Nicotinic Acetylcholine Receptor *Muscarinic acetylcholine receptor
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The GABA Receptor *GABA B receptors are coupled to an intracellular G-protein and act by increasing conductance of an associated K + channel. ReceptorGABA A GABA B GABA C Effector Chloride channel G i/o Chloride channel Agonists Muscimol, THIP Baclophen- Antgonist s BicucullinSaclofen-
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Psychoactive drugs and GABA receptors inhibitory Cl - channels a GABA A receptor two GABA-binding sites (αβ) a benzodiazepine- binding site(αγ) barbiturates-binding sites(αβ)
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The Glutamate Receptor excitatory cation channels: Na +, K +, and Ca 2+ kainate receptor, quisqhalate A receptor AMPA ( -amino-3-hydroxyl-5-methyl-4- isoxazole-propionate) receptor NMDA (N-methyl-D-aspartate) receptor permeable to responsible for basal excitatory synaptic transmission and many forms of synaptic plasticity such as long-term potentiation (LTP) and long-term depression (LTD), which are thought to underlie learning and memory. *quisqualate B receptor: activation of a PI-linked second messenger pathway
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The signaling events on long-term potentiation
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Calcium as a Second Messenger Calcium as a Second Messenger
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Ca 2+ Influx and Efflux Ca 2+ Influx Ca 2+ Influx By gated Ca 2+ channels in plasma membranes By gated Ca 2+ channels in plasma membranes By Ca 2+ channels in intracelluar organelles (ER, SR) By Ca 2+ channels in intracelluar organelles (ER, SR) Ca 2+ Efflux Ca 2+ Efflux By Ca 2+ -ATPase in plasma membranes By Ca 2+ -ATPase in plasma membranes By Ca 2+ -ATPase in intracelluar organelles (ER, SR) By Ca 2+ -ATPase in intracelluar organelles (ER, SR) By accessory Ca 2+ pumps (Ca 2+ /Na + antiporter) By accessory Ca 2+ pumps (Ca 2+ /Na + antiporter)
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IP3- and DAG-mediated Signaling Activation of Gq Activation of Gq → interaction of G qα -subunit with phospholipase C-β (activation) → hydrolysis of phosphoinositol biphosphate (PIP 2 ) to inositol triphosphate (IP 3 ) and Diacylglycerol (DAG) → IP 3 binding to IP 3 receptors (a gated Ca 2+ channel) of ER → intracellular Ca 2+ release →→ activation or inhibition of target proteins Recovery of the intracellular Ca 2+ level Recovery of the intracellular Ca 2+ level Ca 2+ ATPases: pumping out of cytoplasm Ca 2+ ATPases: pumping out of cytoplasm dephosphorylation of IP 3 by a phosphatase dephosphorylation of IP 3 by a phosphatase
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Activity of PI 3-Kinase
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Hydrolysis of PIP 2
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Activation of Phospholipase C-β by G Protein (G q )-coupled receptors
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Ca 2+ Mobilization by IP 3
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Activation of Phospholipase C-γ by Protein-Tyrosine Kinases
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Function of Calmodulin Adenylate cyclase isozymes, cAMP phosphodiesterases,
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Ca 2+ Influx and Neurotransmitter Release
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Ca 2+ influx and exocytosis of synaptic vesicles
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Rizo and Sudhof 2002, Nature Rev. Neurosci.
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Axo-axonic synapse
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Signaling Events on Long-term Potentiation
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Regulation of Intracellular Ca 2+ in Electrically Excitable Cells
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Activation of the Akt protein Kinase - The serine/threonine protein kinase Akt/PKB is the cellular homologue of the viral oncogene v-Akt and is activated by various growth and survival factors (Akt1, Akt2, and Akt3). - PI3K generates phosphorylated phosphatidylinositides (PIP2, PIP3) that bind to Akt. - PIP2 and PIP3 also activate PDK which phosphorylates Akt. - Activated Akt promotes cell survival through two distinct pathways: 1) Akt inhibits apoptosis by phosphorylating the Bad component of the Bad/Bcl- XL complex. 2) Akt activates IKK-a that ultimately leads to NF-kb activation and cell survival.
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Integrin Signaling
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Apoptosis
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Regulators and Effectors of Apoptosis
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Cell Death Receptors
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The PI 3-Kinase Pathway and Cell Survival
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