chapter 16 cont

• Protein kinases


  Proteins involved in the signaling cascades

  
• PKA


  Protein kinase A activated by cyclic AMP
• PKC


  Protein kinase C activated by Ca2+
• CaM K


  Kinase activated by activated Ca2+ bound calmodulin
• 1. PROTEIN-COUPLED RECEPTORS


  A GPCR Signaling Pathway Generates a Dissolved Gas That Carries a Signal to Adjacent Cells

  
• Nitric oxide (NO) signaling

  1. NO binds to guanylyl cyclase

  2. Formation of cyclic GMP

  3. Increase in cyclic GMP

  4. Muscles relax, allowing vessel dilation and increased blood flow

  
• Viagra enhances penile erection by blocking degradation of cyclic GMP, prolonging the NO signal
• The principal action of nitroglycerin is vasodilation or the widening of the blood vessels

  
• Enzyme Linked Receptors


  Has intrinsic enzymatic activity or associates with an enzyme
• Activation of an RTK

  1. Dimerization

  2. Cross-phosphorylation

  3. Assembly of an intracellular signaling complex

  
• Enzyme-linked receptors


  • Play roles in responses to extracellular signals that regulate cell growth, cell proliferation, cell differentiation, cell survival
  • Also mediate cytoskeleton reconfiguration - cell shape, cell movement

  
• Enzyme-linked Receptors


  • Most signals act as local mediators, acting at low concentrations
  • Responses are slow (hours)
  • Require many intracellular signal transduction that eventually lead to changes in gene expression
  • Largest class are the Receptor Tyrosine Kinases (RTK)

  
• Activated RTK


  1. Assemble a complex of intracellular signaling proteins

  2. Activate and coordinate numerous biochemical changes to trigger a complex response such as cell proliferation

  
• Signaling proteins recruited and activated by activated RTKs

  • Phospholipase C - activating phosphatidyl inositol signaling pathway
  • Ras - a small monomeric GTP-binding protein
  • Phosphoinositide 3-kinase (PI 3-kinase)

  
• Ras


  • Small protein bound to the plasma membrane by a lipid tail
  • Monomeric GTP binding protein (GTPase)

  
• MAP-kinase cascade


  Stimulates cell proliferation, survival and induces cell differentiation

  
• 30% of human cancers contain mutations in Ras gene, resulting in Ras that is stimulated all the time (absence of GTPase activity)
• Both GPCRs and RTKs activate multiple intracellular signaling pathways

  
• Signaling pathways can be highly interconnected to enable the cells to produce an appropriate response to a complex combination of signals

  
• Plant Signaling


  • Make use of membrane embedded cell surface receptors, especially enzyme-linked receptors, mostly receptor serine/threonine kinases
  • Do not use receptor tyrosine kinase, steroid hormone type nuclear receptors or cAMP; use few GPCRs
• Plant Signaling


  • Seem to use few G-protein linked receptors
  • Their receptors are structurally different from that of animals
  • Cell–cell communication evolved independently in plants and animals
• Ethylene signaling in plants

  • Ethylene receptors function as histidine kinases
  • Activated ethylene receptors activate a MAP-kinase signaling cascade

  
• In most plant receptor kinases, the signal transduction pathway is not yet fully elucidated

  
• In plants, signals act to relieve inhibition
• Enzyme-coupled Receptors


  • Protein Kinase Networks Integrate Information to Control Complex Cell Behaviors
  • Cell–Cell Communication Evolved Independently in Plants and Animals