1. Lecture 02 – Overview of Signal Transduction Pathways BIOL 5190/6190 Cellular & Molecular Singal Transduction Prepared by Bob Locy Last modified -13F

2. Introduction 1.Molecular Signaling Pathways Electrical Signaling Electrical Signaling Chemical Signaling Chemical Signaling 2.Chemical Signaling Extracellular signaling Extracellular signaling Intracellular signaling Intracellular signaling 3.Cellular Integration of molecular signaling pathways

3. Cell Communication Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 1.Electrical Signaling can involve cells in direct contact, typically via gap junctions. 2.The electrical signals generated can drive intercellular communication via small molecules, including metabolites and electrolytes. 3.Usually associated with excitable membrane systems, e.g. mammalian brain and heart, but may also be part of transmembrane trafficking in other unicellular and multicellular organisms

4. Cell Communication Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 1.More generally communication between cells in multicellular organisms, or sometime in aggregates of unicellular organisms involves communication using chemical signals. 2.Such chemical communication typically involves chemicals produced in one cell that work at a distance, and produce response in a second cell. This is the definition of a hormone. 3.Other factors which may or may not fit the definition of a hormone may also be produced locally and act locally, sometimes within the same cell. 4.Larger (typically peptide/protein) molecules involved in signaling, do not readily cross the plasma membrane, and work through receptors at the cell surface. While smaller molecules can act either extracellularly, or depending on their character, they may enter the cell and act intracellularly.

5. 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. 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. 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. 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. 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.

6. 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

7. Module 1: Figure stimuli for cyclic AMP signalling Module 1: Figure stimuli for cyclic AMP signalling Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012

8. Module 1: Figure stimuli for InsP3/DAG signalling Module 1: Figure stimuli for InsP3/DAG signalling Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012

9. Module 1: Figure stimuli for enzyme-linked receptors Module 1: Figure stimuli for enzyme-linked receptors Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012

10. Module 1: Figure tyrosine kinase-linked receptors Module 1: Figure tyrosine kinase-linked receptors Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012

11. Module 1: Figure PDGFR activation Module 1: Figure PDGFR activation Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012

12. Integrin Signaling Overview

13. Intracellular Receptors 1.Nuclear receptors 2.Cytoplasmic receptors 3.Steroid hormones 4.Other lipophillic horomones, e.g. vitamins

14. Module 1: Figure steroid stimuli Module 1: Figure steroid stimuli Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012