Chapter 9 Cell Signaling PDF

Chapter 9 Cell Signaling 4 Requirements for Signaling: 1. 3. 2. 4. Communication between Cells in Multicellular Life 1. Signaling cell—ex, cells in adrenal glands 2. Signaling molecule—ex, adrenaline...

Chapter 9 Cell Signaling 4 Requirements for Signaling: 1. 3. 2. 4. Communication between Cells in Multicellular Life 1. Signaling cell—ex, cells in adrenal glands 2. Signaling molecule—ex, adrenaline 3. Receptor protein—ex, on cells of organs 4. Responding cell— example, cells causing physiologic changes like increased heart or breathing rate  Communication in Bacterial Cells: Uptake of DNA from the Environment Cell Signaling Steps Use the numbered terms listed to fill in the blanks of the following statement: In communication between cells, the _____ produces the signaling molecule, also known as the _____; the _____ produces the _____, to which the signaling molecule binds. 1. ligand A) 2; 1; 4; 3 2. signaling cell B) 1; 2; 3; 4 3. receptor C) 2; 3; 1; 4 4. responding cell D) 4; 3; 2; 1 Signals Can Travel Short and Long Distances Endocrine Signaling – Long Distance Signaling Mainly molecules traveling through the bloodstream. (ex, Estrogen and testosterone) Paracrine Signaling - Small, Water-Soluble Signals that Move to Neighboring Cells Growth factors are types of paracrine signaling molecules.  Growth Factors Promote Cell Growth Cells grow well in the presence of blood serum, but not as well in blood plasma due to presence of something called Platelet-Derived Growth Factor (PDGF) Autocrine Signaling – Signaling and Responding Cell are the Same Important during embryonic development. Contact-Dependent: Transmembrane Protein in One Cell is Signal, Binds to Receptor on Another Example is Delta- Notch signaling in development Undifferentiated cells with Delta contact those with Notch become neurons, Notch cells become glial cells Consider the following scenario: You observe a cell that has a receptor protein that binds a signaling molecule that is produced by the same cell. What kind of signaling is occurring in this cell? A. autocrine signaling B. contact-dependent signaling C. paracrine signaling D. endocrine signaling In a normal, healthy cell, what is the BEST reason that paracrine signaling does not activate the responding cell? A. Responding cell’s receptors have a mutation. B. Neighboring cells are usually too far away for paracrine signaling C. Concentration of the signaling molecule is too high. D. The responding cell does not have the proper receptor.  Receptors – Proteins that Bind Signaling Molecules Found inside cell or on cell surface as a membrane-bound protein. Signaling molecules = ligand. Ligands bind to the ligand-binding site of 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 Molecules (Steroid Hormones) Can Cross Membrane and Bind in Cytoplasm or Nucleus  Cell-Surface Receptors – Polar Ligands Can’t Cross the Membrane and Instead Bind to Surface Receptors Cell-surface receptor/ligand complex undergoes a conformational change and the receptor is activated. You isolate a cell and strip off proteins on the cell’s surface using a protease. You then add a specific signaling molecule. The cell responds. How did this cell respond? A. Receptor is a ligand-gated ion channel. B. Signal does not need a receptor. C. Signal can directly activate second messengers and does not need to activate the receptor. D. The receptor for this signal is inside the cell, and the signaling molecule is nonpolar and can diffuse into the cell.  3 Types of Cell Surface Receptors Thousands of different proteins exist on surface of any given cell. The proteins involved in cell signaling can be classified into three main groups: 1. G protein-coupled receptors 2. receptor kinases 3. ion channels G Protein-Coupled Receptor – Inactive until Bound Once ligand binds, it can bind the G protein. G protein-coupled receptor is active when ligand is bound to the receptor and the receptor has bound the G protein.  G Protein Activation – Ligand Binding Activates Receptor, which binds G Protein  Heart Muscles Stimulated by G Proteins A second messenger cAMP transmits signal from G protein to inside cell. Protein kinase A activates other proteins in cell, so response to the signal inside the cell is complete. Amplification of Adrenaline Signal Each adrenaline- bound receptor activates multiple G proteins. Each adenylyl cyclase produces LOTS of cAMP (second messenger). Each active protein kinase A activates multiple proteins.  G Protein Signal Termination When concentration of adrenaline eventually wanes, adrenaline will diffuse from receptor and receptor will revert to inactive form. Receptor no longer activates G protein, GTP is converted to GDP, and adenylyl cyclase no longer produces second messenger cAMP.  The Role of Phosphatases Enzymes in 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 Ligand Binds, Receptor Kinase Dimerizes and Phosphorylates Another Protein Insulin, wound healing  Receptor Kinase Activation and Signaling  MAP Kinase and the Ras/Raf/Mek/Erk Protein Cell repair started via PDGF from damaged cells. PDGF binds its receptor, dimerization occurs Phosphorylated receptors activate proteins in cell. In MAP kinase pathway, the protein Ras is activated. MAP Kinase Pathway GTP-bound Ras triggers a kinase cascade. Activated kinase enters 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.  Ligand-Gated Ion Channel Ion channels alter flow of ions across membrane. When ligand binds an ion channel, the ion channel opens and ions can flow across the cell membrane.  Cell Signaling and Cancer Some cancers can form when a signaling molecule is overproduced or produced in altered forms. Mutations that make Ras always bound to GTP, cause 30% of all cancers - 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. Which answer choices could account for the increased cell proliferation in the patient? A. None of the other answer options is correct. B. Concentration of a signaling molecule in the patient is higher than usual. C. Cells taken from the patient exhibit a reduced level of signal amplification. D. Cells taken from the patient have fewer growth factor receptors than normal.  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.  GDP  GTP RAF MEK Adenyl Cyclase ERK Nuclear – changes gene expression