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