F24 Gen Bio I Chap 9 - Cell Signaling - Student Version (1) PDF

Chapter 9 Cell Signaling  Student Learning Outcomes – Signaling 11a. Know the steps of signal transduction 11b. Describe how cells communicate with each other, depending on the distance 11c. Know the different types of receptors (cell surface vs intracellular) 11d. Describe...

Chapter 9 Cell Signaling  Student Learning Outcomes – Signaling 11a. Know the steps of signal transduction 11b. Describe how cells communicate with each other, depending on the distance 11c. Know the different types of receptors (cell surface vs intracellular) 11d. Describe the major activation events of GPCRs and receptor kinases and how their signaling is amplified and attenuated  Essential Elements for Communication 1. Signaling cell 2. Signaling molecule 3. Receptor molecule 4. Receptor cell Communication Among Four essential elements of Cells cellular communication are the in a Multicellular following: Organism 1. signaling cell—example, cells of the adrenal glands 2. signaling molecule— example, cells of adrenaline 3. receptor protein—example, cells of organs 4. responding cell—example, cells causing physiologic changes such as increased heart rate or breathing rate Steps in Cell Signaling Signaling Over Long and Short Distances Endocrine Signaling Some signaling molecules may need to travel great distances in the body through the circulatory system. Signaling by means of molecules traveling through the bloodstream is called endocrine signaling. Estrogen and testosterone are examples of endocrine signaling molecules.  Paracrine Signaling Signaling molecules from one cell can move to another cell through diffusion. Paracrine signals are typically small and water soluble. Growth factors are types of paracrine signaling molecules. Autocrine Signaling In autocrine signaling, both the signaling and responding cell are the same cell. Autocrine signaling, in addition to paracrine signaling, can be important during embryonic development.  Contact-Dependent Signaling Contact-dependent signaling occurs when a transmembrane protein in one cell acts as the signal and binds to a receptor protein on an adjacent cell.  Signaling Molecules and Receptors Receptors are proteins that bind signaling molecules. Receptors can be found inside the cell or presented on the cell surface as a membrane- bound protein. Signaling molecules are referred to as a ligand. Ligands bind to the ligand-binding site of the receptor. When ligands bind the receptor, there is a change in conformation of the receptor, and we say the receptor is activated.  Intracellular Receptors Nonpolar signaling molecules (e.g., steroid hormones) are able to cross the cell membrane and bind an intracellular receptor in the cytoplasm or nucleus.  Cell-Surface Receptors Polar signaling molecules cannot cross the cell membrane and instead bind to transmembrane proteins that are cell-surface receptors. Once bound to its ligand, the cell-surface receptor/ligand complex undergoes a conformation change and the receptor is activated.  Major Types of Cell-Surface Receptors There can be thousands of different proteins on the surface of any given cell. Many of the proteins involved in cell signaling can be classified into two major groups: 1. G protein-coupled receptors 2. receptor kinases  G Protein-Coupled Receptor A G protein-coupled receptor is inactive until the ligand binds. Once the ligand binds the receptor, it is able to bind the G protein. The G protein-coupled receptor is active when the ligand is bound to the receptor and the receptor has bound the G protein. G Protein Activation When the ligand binds the receptor, the receptor activates and can bind the G protein. When the G protein binds to the activated receptor, GDP is replaced with GTP on the alpha subunit of the G protein. The alpha subunit disassociates from the other subunits and then binds to the target protein to activate the protein. Chapter 9 Active Lecture Slide 31 Adrenaline: An Example of GPCR Signaling Heart muscles are stimulated through G protein activation. The second messenger cAMP transmits the signal from the G protein to inside the cell. Protein kinase A activates other proteins in the cell, so the response to the signal inside the cell is complete. Amplification of Adrenaline Signal Each adrenaline- bound receptor activates multiple G proteins. Each adenylyl cyclase molecule produces large amounts of cAMP (second messenger). Each active protein kinase A activates multiple protein targets.  All Signaling Must End: G Protein Signal Termination (Attenuation) When the concentration of adrenaline eventually wanes, adrenaline will diffuse off of the receptor and the receptor will then revert to its inactive form. The receptor no longer activates the G protein, GTP is converted to GDP, and adenylyl cyclase no longer produces the second messenger cAMP.  G Protein Signal Termination: The Role of Phosphatases Enzymes in the cytosol degrade cAMP, which stops the activation of more protein kinase A molecules. Phosphatases remove phosphate groups from activated proteins, making them inactive.  Receptor Kinase When a ligand binds the ligand-binding site, the receptor kinase becomes active, phosphorylating another protein and transmitting the signal from outside the cell to inside the cell. Receptor Kinases  Receptor Kinase Activation and Signaling  The MAP Kinase Pathway: Activating the Ras Protein When we get a small paper cut, cells need to be repaired. Cell repair is stimulated by the release of platelet-derived growth factor (PDGF) from damaged cells. PDGF binds to its receptor, and the receptors dimerize and become active. The phosphorylated receptors help activate other proteins in the cell. In the MAP kinase pathway, the cytoplasmic signaling protein Ras is activated.  The MAP Kinase Pathway GTP-bound Ras triggers a kinase cascade. An activated kinase enters the nucleus where expression of genes associated with cell division is turned on. Termination of this pathway occurs when GTP is replaced by GDP on Ras.  Cell Signaling and Cancer Some cancers can form when a signaling molecule is overproduced or produced in altered forms. Mutations in Ras, where it is always bound to GTP, cause 30% of all cancers. These mutations stimulate cell division and can result in tumor formation. Some cancers can be caused when a receptor remains bound to its ligand. An excess of receptors can also cause cancer because there is an increase in cellular response.  Integration of Signaling Pathways Focusing on one single pathway at a time helps us understand the control of that pathway. In the context of the cell, one pathway may stimulate a cellular response and also inhibit another signaling pathway. Different pathways may also have different effects in different organisms. For example, in mammalian cells, the MAP kinase pathway promotes cell division, whereas in yeast cells, it triggers sexual reproduction.