JP

Chapter 13 - Signaling at the Cell Surface

13.1: Signaling Molecules and Cell-Surface Receptors

  • Extracellular signaling molecules are essential regulators for developing the interactive components of unicellular organisms and aid in the development of growth and physiology of multicellular organisms
  • Extracellular signaling molecules binding to the cell surface help with the guidance of cellular metabolism, gene expression, and function
  • These are the external signals that cells detect:
    • Membrane anchored and secreted proteins and peptides
    • Lipophilic molecules
    • Steroid hormones
    • Thyroxine
    • Amino acid molecules
    • Epinephrine
    • Gases
    • Nitric oxide
    • Physical stimuli
    • Light
  • Paracrine:
    • When signals from one cell affect cells directly around it
  • Endocrine:
    • When signals from one cell affect distant cells
  • Autocrine
    • When signals affect the cell itself

13.2: Intracellular Signal Transduction

  • Nonprotein intracellular signaling molecules help with the regulation of enzymatic and nonenzymatic proteins
  • Monomeric proteins, trimeric proteins, phosphates, and protein kinases all help with transporting and regulating signals
  • When receptors and proteins cluster together, they form lipid rafts, which promote the interaction between signaling proteins and this enhances signal transduction

13.3: G Protein-Coupled Receptors That Activate or Inhibit Adenylyl Cylacase

  • Trimeric G proteins convert into effector proteins, which help with either becoming another form of messengers or channel proteins in the cells
  • The signals switch between on (GTP) and off (GDP)
  • Hormone occupied receptors initiate the binding of GTP in the cell, causing Ga to interact with an effector protein
  • Characteristics of PKA:
    • cAMP-dependent activation of protein kinase A
    • Substrates for PKA
    • PKA activation is hormone-induced
    • Its activation is varied among cells
  • PKA has two effects on liver and muscle cells:
    • Inhibit glycogen synthesis
    • Stimulate glycogen breakdown
  • Second messengers and kinase cascades help make signaling pathways more powerful

13.4: G Protein-Coupled Receptors That Regulate Ion Channels

  • The activation of receptor GPCR opens the K+ channels, which causes a hyperpolarization that slows down the rate of heart muscle contraction
  • The binding of GTP to Gta changes the proteins which hinder interactions with Gby
  • Light-activated ospin and the binding of arrestin to phosphorylated ospin activate transducin,
  • This adaption is used by GPCRs at high ligand levels

13.5: G Protein-Coupled Receptors That Activate Phospholipase C

  • Simulation of cell surface receptors such as GPCRs, help lead to the activation of phospholipase C. This generates two new second messengers:
    • Diffusable IP3
    • Membrane-Bound DAG
  • IP3 and Ca2+ channels:
    • IP3 opens IP3-gated Ca2+ channels in the endoplasmic reticulum
    • It also leads to the elevation of the Ca2+
    • Because of this elevation, protein kinase C is formed
  • This protein is activated by DAG
  • Ca2+/calmodulin complex helps with the regulation of many different proteins:
    • cAMP phosphodiestrase
    • Nitric oxide synthase
    • Protein kinases or phosphates
  • cGMP synthesis leads to protein kinase G being activated in vascular smooth muscle cells, which help with the muscles relaxation

13.6: Activation of Gene Transcription by G Protein-Coupled Receptors

  • Tubby transcription factor:
    • Phospholipase C is coupled to G proteins to release this factor
  • This factor is bound to the PIP2 embedded in resting cells plasma membranes
  • Kinase A (PKA) can lead to phosphorylation of CREB protein, and with the CBP/300 coactivator, can cause the transcription of target genes
  • GPCR-arrestin complex initiates cytosolic kinases, and those cascades lead to the activation of cell growth controlling genes