Receptor Tyrosine Kinases (RTKs) Overview
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Questions and Answers

What is the role of phosphorylated tyrosine residues in Receptor Tyrosine Kinases (RTKs)?

  • They catalyze the degradation of the receptor.
  • They act as docking sites for adapter proteins. (correct)
  • They serve as binding sites for signaling molecules.
  • They inhibit kinase activity.

    • Which protein is mentioned as an example that binds through the SH2 domain to activated RTKs?

  • Grb2 (correct)
  • PI3 kinase
  • IRS1
  • Src

    • What initiates the activation of intracellular signaling in Receptor Tyrosine Kinases?

  • Cross phosphorylation of tyrosine residues (correct)
  • Binding of ligands to the receptor
  • Dissociation of adapter proteins
  • Phosphorylation of target proteins

    • How does the insulin receptor contribute to cellular signaling?

    <p>By autophosphorylating and catalyzing phosphorylation of target proteins</p> Signup and view all the answers

    Which of the following proteins is specifically activated by binding to an activated PDGF receptor?

    <p>PI3 kinase</p> Signup and view all the answers

    What happens to Ras when GTP is bound to it?

    <p>It becomes active.</p> Signup and view all the answers

    Which kinase is directly activated by Ras?

    <p>raf-1 MAP kinase kinase kinase</p> Signup and view all the answers

    What is the primary role of MEK in the kinase cascade?

    <p>To phosphorylate MAPK.</p> Signup and view all the answers

    What effect does the phosphorylation of transcription factors like fos and jun have?

    <p>They bind to DNA and alter gene transcription.</p> Signup and view all the answers

    What is the significance of the kinase cascade initiated by Ras?

    <p>It creates a signal amplification mechanism.</p> Signup and view all the answers

    What role does AKT play in cellular metabolism?

    <p>Increases the activity of Glut4</p> Signup and view all the answers

    Which component directly activates Ras in the signaling pathway?

    <p>GEF</p> Signup and view all the answers

    What is the primary function of the GAP protein in the Ras signaling pathway?

    <p>Increases intrinsic GTPase activity</p> Signup and view all the answers

    Which of the following statements about receptor tyrosine kinases (RTKs) is correct?

    <p>RTKs act as signal transducers for multiple pathways.</p> Signup and view all the answers

    What is a major consequence of persistent activation of Ras due to dominant mutations?

    <p>Enhanced cellular division and potential cancer formation</p> Signup and view all the answers

    Which statement accurately describes the PI3 kinase signaling pathway?

    <p>It is involved in the activation of AKT.</p> Signup and view all the answers

    What is the outcome of MAP kinases phosphorylating transcription factors?

    <p>Regulation of cell cycle and differentiation</p> Signup and view all the answers

    How are protein kinase cascades advantageous in signal transduction?

    <p>Amplifies the signal at multiple stages.</p> Signup and view all the answers

    What is the initial event that occurs upon ligand binding to a Receptor Tyrosine Kinase (RTK)?

    <p>Autophosphorylation of the receptor</p> Signup and view all the answers

    What is true about the structure of most Receptor Tyrosine Kinases?

    <p>They have an extracellular ligand binding domain and a cytosolic kinase domain.</p> Signup and view all the answers

    Which of the following ligands can cross bind to Receptor Tyrosine Kinases?

    <p>Insulin and Insulin-like Growth Factor 1 (IGF1)</p> Signup and view all the answers

    What is the role of heterodimerization in the activation of Receptor Tyrosine Kinases?

    <p>It initiates changes that lead to kinase activation.</p> Signup and view all the answers

    Which statement is true concerning ligand shedding in RTK signaling?

    <p>It is mediated by proteases that cleave the ligand.</p> Signup and view all the answers

    What consequence does receptor dimerization have on RTKs?

    <p>It triggers cross-phosphorylation of the receptors.</p> Signup and view all the answers

    What defines the unique function of Receptor Tyrosine Kinases compared to other receptor types?

    <p>They have intrinsic kinase activity that facilitates phosphorylation.</p> Signup and view all the answers

    What is commonly found in the structure of Receptor Tyrosine Kinases?

    <p>An N-terminal extracellular ligand binding domain.</p> Signup and view all the answers

    Which biological processes are commonly associated with Receptor Tyrosine Kinases?

    <p>Regulation of growth and differentiation.</p> Signup and view all the answers

    What type of signaling process is initiated following ligand-receptor interaction in RTKs?

    <p>Propagation of intracellular signaling cascades</p> Signup and view all the answers

    What initiates the activation of Ras in the signaling pathway?

    <p>Exchange of GDP for GTP by Sos</p> Signup and view all the answers

    Which domain of the GRB2 protein allows it to bind to receptor phosphotyrosine residues?

    <p>SH2 domain</p> Signup and view all the answers

    What role does the protein Sos play in the activation of Ras?

    <p>It acts as a GEF to promote GDP-GTP exchange</p> Signup and view all the answers

    How does the activated Ras-GTP complex affect downstream signaling?

    <p>It activates the MAP kinase pathway</p> Signup and view all the answers

    What happens to the Ras protein after it is activated by Sos?

    <p>It dissociates from Sos but remains membrane-tethered</p> Signup and view all the answers

    Which of the following correctly describes the process of receptor activation by EGF?

    <p>Receptor dimerization leads to autophosphorylation on tyrosine residues</p> Signup and view all the answers

    What is a primary function of Ras in signaling pathways?

    <p>To amplify signals sent from the receptor</p> Signup and view all the answers

    How does the activation of receptor tyrosine kinases influence the SH2 domain protein interactions?

    <p>It creates a binding site for proteins with SH2 domains</p> Signup and view all the answers

    Study Notes

    Receptor Tyrosine Kinases (RTKs)

    • RTKs are cell surface receptors directly linked to intracellular enzymes (kinases)
    • Many growth factor receptors are part of this family, including PDGF, NGF, EGF, FGF, VEGF, insulin, and IGF1
    • Receptors can be single polypeptides or dimers (two single peptides that dimerize upon ligand activation)

    Learning Outcomes

    • This lecture introduces the tyrosine kinase-linked receptors (RTKs)
    • Includes ligand binding and receptor activation
    • Describes signal initiation and transmission (players)
    • Explains diverse functions of RTKs
    • Investigates implications in biological processes

    Overview of RTKs: Family Members

    • Insulin and IGF1 can cross-bind
    • Includes receptors like EGF, insulin, IGF-1, NGF, FGF, PDGF, M-CSF, VEGF, Eph receptor
    • Each type has its own unique domains (e.g., cysteine-rich, tyrosine kinase, immunoglobulin-like)

    Overview of RTKs: Structure

    • RTKs have an extracellular ligand-binding domain
    • A single-pass transmembrane α-helix
    • A cytosolic C-terminal domain with intrinsic tyrosine kinase activity
    • Ligand binding triggers autophosphorylation of the receptor

    Mechanism of Activation: Receptor-Ligand Binding

    • Ligands form dimers through disulfide bonds
    • Ligands bind to two identical receptor binding sites
    • Binding of the hormone causes receptor dimerization
    • Initiates intracellular signaling

    Mechanism of Activation: Receptor Dimerization and Kinase Activation

    • Receptor dimerization leads to autophosphorylation
    • Each receptor cross-phosphorylates a specific tyrosine residue on its counterpart
    • Activation of its kinase activity

    Mechanism of Activation: Docking of signaling molecules at RTK

    • Phosphorylated tyrosine residues on RTKs become docking sites for adapter proteins
    • These adapter proteins can be proteins like Grb2, which have SH2 domains

    Mechanism of Activation: The Binding of SH2-containing signaling proteins

    • Phosphorylated tyrosines can be specifically identified by SH2 domains on other proteins, including adapter proteins
    • Activated receptors can phosphorylate these bound proteins
    • This leads to intracellular signal transmission

    Initiation of Cellular Response

    • 2 insulin molecules bind and induce a conformational change in the receptor
    • Autophosphorylates and catalyzes phosphorylation of target proteins like IRS1
    • Initiates multiple cellular responses (e.g., insulin signaling activates glucose transport)

    Transduction of Response

    • Protein kinase cascades amplify signals at each step
    • Information received at the plasma membrane is communicated to the nucleus
    • Multiple steps in the pathway provide specificity
    • Various target proteins provide diversity in response

    RTK Signaling: Ras Pathway

    • Ras is a monomeric GTPase switch protein
    • Activation is enhanced by GEF (guanine nucleotide exchange factor)
    • GDP-GTP exchange leads to activation
    • Deactivation requires GAP (GTPase-activating proteins) that increase intrinsic GTPase activity
    • Once active, Ras propagates signaling through a MAP kinase cascade
    • Mutant RTKs or Ras/MAP kinase signaling proteins are linked with nearly all cancers

    Ras activation mechanism

    • EGF binding causes receptor dimerization and autophosphorylation
    • GRB2 binds to phosphorylated tyrosines; GRB2 contains SH3 domains that allow SOS protein to bind to the membrane complex
    • SOS then recruits Ras to the complex
    • SOS promotes GTP exchange for GDP on Ras
    • Active Ras-GTP complex dissociates from Sos
    • Active Ras then activates the MAP kinase portion of the signaling pathway

    Mechanism of Tyrosine Kinase Receptors

    • Hormone binding causes receptor dimerization/aggregation
    • Receptor tyrosine kinase domains phosphorylate C-terminal tyrosines
    • Phosphorylation produces binding sites for proteins with SH2 domains (e.g., GRB2 with bound SOS)
    • SOS is a GEF that activates Ras by exchanging GDP for GTP
    • Activated Ras activates Raf-1 kinase, MEK, and MAPK kinase, resulting in a kinase cascade
    • Kinase cascade triggers changes in gene expression which regulate protein activity

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    Bioc 325 Lecture 10: Receptor Tyrosine Kinases (RTKs)

    Description

    This quiz provides an in-depth look at receptor tyrosine kinases (RTKs), their structure, and functions. Learn about the various types of RTKs including growth factor receptors, their mechanism of action, and implications in biological processes. Perfect for understanding the role of RTKs in cell signaling.

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