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Questions and Answers

What is the primary role of adenylyl cyclase in signal transduction?

  • To synthesize G-proteins
  • To trigger the release of pyrophosphate
  • To hydrolyze ATP into ADP
  • To convert ATP into cyclic AMP (correct)

    • Which molecule is formed when cyclic AMP is hydrolyzed?

  • Adenosine triphosphate
  • Cyclic diphosphate
  • 5'-adenosine monophosphate (correct)
  • Cyclic guanosine monophosphate

    • Who conducted seminal research that identified cyclic AMP as a key molecule in signal transduction?

  • Mendel
  • Watson and Crick
  • Koshland
  • Sutherland (correct)

    • What is the significance of the particulate fraction in Sutherland's experiments?

    <p>It released cyclic AMP when activated by hormones</p> Signup and view all the answers

    How many different Gα subunits are encoded by the genes discussed?

    <p>21 different subunits</p> Signup and view all the answers

    What is the first step in the cell signaling process?

    <p>Synthesis of the signaling molecule</p> Signup and view all the answers

    Which type of signaling involves messenger molecules reaching target cells via the bloodstream?

    <p>Endocrine signaling</p> Signup and view all the answers

    What is the role of the ligand once it binds to its receptor?

    <p>It causes a conformational change in the receptor</p> Signup and view all the answers

    What type of receptor is primarily involved in signaling molecules that cannot cross the plasma membrane?

    <p>Cell-surface receptors</p> Signup and view all the answers

    What occurs after the binding of a ligand to a receptor?

    <p>Initiation of one or more intracellular pathways</p> Signup and view all the answers

    Which type of signaling involves cells that have receptors on their surface responding to the same messenger they produce?

    <p>Autocrine signaling</p> Signup and view all the answers

    Which of the following is NOT a type of cell-surface receptor?

    <p>Intracellular receptors</p> Signup and view all the answers

    What is a characteristic of juxtacrine signaling?

    <p>Requires physical contact between sending and receiving cells</p> Signup and view all the answers

    What role do second messengers play in cellular signaling?

    <p>They enhance or reduce concentrations in response to first messengers.</p> Signup and view all the answers

    What is the primary function of protein kinase A (PKA)?

    <p>To phosphorylate target proteins on specific amino acids.</p> Signup and view all the answers

    How does PKA recognize which substrates to phosphorylate?

    <p>By the specific cell type and the corresponding stimulus.</p> Signup and view all the answers

    What is the purpose of kinase anchoring proteins (AKAPs)?

    <p>To confine PKA signaling to specific cellular locations.</p> Signup and view all the answers

    Which substrates does PKA primarily phosphorylate?

    <p>Serine and threonine residues on target proteins.</p> Signup and view all the answers

    What is one function of AKAP5 as described in the content?

    <p>It functions as a scaffold protein in signaling hubs.</p> Signup and view all the answers

    Why is the confinement of the PKA signaling process important?

    <p>To allow relevant substrates to be phosphorylated first.</p> Signup and view all the answers

    How many different AKAPs have been discovered according to the information provided?

    <p>At least 50</p> Signup and view all the answers

    What role do AKAPs play in the context of PKA signaling?

    <p>They help localize PKA to specific substrates.</p> Signup and view all the answers

    What type of mutations can lead to disorders associated with G protein-coupled receptors?

    <p>Both loss and gain of function mutations.</p> Signup and view all the answers

    How do gain of function mutations in G proteins affect cellular signaling?

    <p>They create a constitutively activated G protein.</p> Signup and view all the answers

    What is the role of adenylyl cyclase in relation to cAMP?

    <p>It generates cAMP from ATP.</p> Signup and view all the answers

    What relationship exists between cAMP and PKA?

    <p>cAMP activates PKA by binding to it.</p> Signup and view all the answers

    Which statement correctly describes first and second messengers in signaling pathways?

    <p>First messengers activate receptors on the cell surface; second messengers transmit signals intracellularly.</p> Signup and view all the answers

    What is the primary function of GRK in the context of GPCR signaling?

    <p>To phosphorylate activated GPCRs for desensitization.</p> Signup and view all the answers

    How can certain polymorphisms in G protein-related genes affect health?

    <p>They may increase susceptibility to some conditions while decreasing it for others.</p> Signup and view all the answers

    What is the role of second messengers in cell signaling pathways?

    <p>They amplify the initial signal received by receptors.</p> Signup and view all the answers

    What molecular change does phosphorylation typically induce in a protein?

    <p>It alters the protein's charge and conformation.</p> Signup and view all the answers

    Which component activates an effector protein in G protein-coupled receptor signaling?

    <p>GTP binding to the alpha subunit.</p> Signup and view all the answers

    What characterizes the conformational change in G protein-coupled receptors upon ligand binding?

    <p>The affinity for G proteins increases significantly.</p> Signup and view all the answers

    What happens during the desensitization of G protein-coupled receptors?

    <p>Active receptors are inhibited from activating G proteins.</p> Signup and view all the answers

    What distinguishes triple-negative breast cancer cells from other cancer cells?

    <p>Higher levels of tyrosine phosphorylation.</p> Signup and view all the answers

    How is GTP involved in the regulation of GTP-binding proteins?

    <p>It hydrolyzes to GDP to deactivate the protein.</p> Signup and view all the answers

    Which proteins are classified as GEFs in G protein signaling?

    <p>Guanine nucleotide exchange factors.</p> Signup and view all the answers

    Which is a characteristic feature of protein kinases?

    <p>They add phosphate groups to hydroxyl groups.</p> Signup and view all the answers

    In which form do G proteins exist when they are inactive?

    <p>Bound GDP in the alpha subunit.</p> Signup and view all the answers

    What common feature is found in most signaling pathways?

    <p>Incorporate the process of phosphorylation.</p> Signup and view all the answers

    What is the function of arrestins in receptor signaling?

    <p>They block active receptors from activating G proteins.</p> Signup and view all the answers

    What type of messengers can act as first messengers in cell signaling?

    <p>Various types including proteins, peptides, and fatty acids.</p> Signup and view all the answers

    What is the primary outcome of signal integration in a cell?

    <p>Triggering different cellular responses.</p> Signup and view all the answers

    Study Notes

    Cell Signaling and Signal Transduction

    • Cell signaling is the process of communication between cells.
    • Extracellular signals elicit a cellular response.
    • Signaling molecules are synthesized, released, travel to a target cell, and bind to a receptor.
    • Receptor binding triggers a response.
    • Receptors initiate one or more intracellular pathways.
    • Cellular function, metabolism, gene expression, shape, and movement can all change as a result of such processes.
    • Receptor deactivation and ligand removal conclude the process.

    Types of Intercellular Signaling

    • Endocrine signaling: Signaling molecules (e.g., insulin) travel through the bloodstream to distant target cells.
    • Paracrine signaling: Signaling molecules travel short distances through extracellular space (e.g., neurotransmitters) to nearby target cells.
    • Autocrine signaling: Cells have receptors that respond to signaling molecules they themselves secrete (e.g., T-cells).
    • Juxtacrine signaling: Signaling molecules remain at the surface of cells, requiring physical contact between sending and receiving cells (e.g., antigen presentation).

    Receptor Location

    • Cell-surface receptors: Hydrophilic signaling molecules bind to receptors on the cell surface.
      • Three major classes: G-protein coupled receptors (GPCRs), enzyme-linked, and ion channel-linked.
    • Intracellular receptors: Small hydrophobic signaling molecules can diffuse across the plasma membrane to bind to intracellular receptors.

    Signaling Pathways

    • Two types:
      • Receptors on or in target cells receive the message.
      • Some cell surface receptors generate soluble, diffusible intracellular second messengers.
      • Second messengers activate or inactivate proteins.
      • Other surface receptors recruit proteins.
    • Many signal transduction pathways combine these mechanisms.

    Second Messengers

    • Small molecules that increase or decrease in concentration in response to a first messenger.
      • Bind to proteins to modify their activity.
    • Examples: Cyclic AMP (cAMP), cyclic GMP (cGMP), 1,2-diacylglycerol (DAG), inositol 1,4,5-trisphosphate (IP3).

    Protein Kinases and Phosphatases

    • Kinases phosphorylate target proteins.
    • Phosphatases dephosphorylate them.
    • Phosphorylation changes a protein’s charge and generally leads to a conformation change.
    • This can increase or decrease ligand binding or other features, altering activity.

    GTP-Binding Proteins

    • GTPase superfamily hydrolyzes GTP to GDP.
    • Two conformations (on and off).
      • on = bound GTP
      • off = bound GDP.
      • GTPase-activating proteins (GAPS), regulators of G protein signaling (RGSs), or guanine nucleotide dissociation inhibitors (GDIs), can influence signal transduction.
    • Guanine nucleotide exchange factors (GEFs) facilitate the exchange between GDP and GTP.

    Molecular Switches

    • Phosphorylation
      • Addition of phosphate groups to hydroxyl groups on serine, threonine, and tyrosine, commonly.
      • Kinases phosphorylate.
      • Phosphatases dephosphorylate
    • GTP-binding proteins
      • Hydrolysis of GTP to GDP can change protein activity.

    Signal Amplification

    • A small amount of ligand can elicit a large cellular response via amplification.
      • Epinephrine can illicit a large cellular response.

    Signal Integration

    • Cells receive many signals.
    • Combinations of signals generate specific responses.

    Survey of Extracellular Messengers and Receptors

    • Receptor location varies:
      • On or in the target cell
    • Ligands vary in the type of molecule.
    • Ligands include ions, enzymes, second messengers, etc.

    Signal Transduction by GPCRs

    • GPCRs have 7 membrane-spanning a-helices.
    • Ligand binding changes receptor conformation which changes the G protein's activity.
    • Different G protein types exist, leading to different responses.

    Termination of Response

    • Desensitization: Blocking receptors from turning on additional proteins (GRK-phosphorylates GPCR).
    • Arrestins: Competing with G proteins for binding to GPCRs.
    • Receptor recycling/internalization: Recycling GPCRs back to the cell surface for continued responsiveness.

    cAMP

    • Second messenger generated by adenyl cyclase.
    • Adenyl cyclase catalyzes the conversion of ATP to cAMP.
    • Protein kinase A (PKA) gets activated by cAMP.

    Discovery of cAMP

    • Sutherland identified a substance released from cell membranes: cAMP.
    • cAMP activates glycogen phosphorylase, involved in glucose mobilization.

    cAMP activates PKA

    • Protein Kinase A (PKA) is known to have many substrates
    • PKA phosphorylates proteins, resulting in phosphorylation of serine, threonine which affects a variety of cellular activities.

    AKAPs

    • Anchoring proteins confine signaling processes, leading to localized effects on target proteins.
    • PKA is confined and is only activated by kinases at specific locations.

    The Human Perspective

    • Many G protein-coupled receptors (GPCRs) are associated with human diseases stemming from mutations, both gain and loss of function type.
    • Ligands that bind to GPCRs are over 1/3rd of the prescription drugs.

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