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