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Cell Signaling (Signal Pathway (GPCR (Example: "fight or flight…

- - - - signal amplification
        
        single molecule activates several G protein molecules
        
        each molecule of adenyl cyclase (catalyzes production of large amounts of cAMP
        
        each PKA molecule activates multiple protein targets by phosphorylation
      - adrenaline = ligand which binds to beta-adrenergic receptors
      - GTP-bound a unit binds to and activates adenylyl cyclase (enzyme in cell membrane)
      - adenylyl cyclase
        
        converts nucleotide ATP --> cyclic AMP (cAMP)
        
        second messenger: signaling molecule found inside cells that relay info to next target in signal transduction pathway
        
        binds to and activates protein kinase A (PKA)
      - Activation of PKA
        
        cAMP --> PKA regulatory subunits separate from PKA catalytic subunits
        
        goes on to break down glycogen
    - - 2 states (on and off)
      - activated by releasing GDP and binding to guanine nucleotides of GTP
      - 3 subunits
        
        alpha subunits binds to either GDP or GTP (when activated, breaks off from other subunits)
        
        gamma and Beta subunits go off and activate other proteins/receptors
  - - - "permission to grow" understood by fibroblasts
        
        platelets release proteins (including PDGF)
        
        PDGF binds to receptor
      - Ras: like the alpha subunit of G-protein; targets of activated receptor kinase
        
        when activated by receptor kinase, exchanges GDP for GTP --> activates kinase --> series of activation (Mitogen-activated protein MAP kinase pathway)
      - Final activated kinase enters nucleus (phosphorylates target proteins)
        
        target proteins = transcription factors (changes in gene expression)
      - signals amplified as signal passed from kinase to kinase
- - - - enough of signal --> cell grows
  - - - response in heart (opening of ion channels)
      - liver cells break down glucagon
  - - - Example: cell has 10 to 100 times normal number of receptors for signaling molecule epidermal growth factor (high gene expression)
    - - prevents Ras from cleaving GTP --> sustained activation of MAP kinase pathway
- - - - Endocrine signaling
      - Function: coordinates multiple organs
      - Example: insulin = regulatory blood sugar levels; adrenaline;
        estradiol and testosterone (travel from ovaries and testes --> breast tissue, etc.
    - - paracrine signaling: signal molecule moves by diffusion
        
        instances when it is important
        
        development (embryo)
        
        within organs (different cell types coordinated together)
        
        signal usually small, water-soluble molecule
        
        Example: growth factor = causes responding cell to grow, divide, or differentiate
        
        communication between neurons: neurotransmitters diffuse across synapse to responding cell (elicits transmittance of nerve impulse)
        
        communication between neurons and muscle cells: muscle cell response = contraction
      - Direct-to-direct contact
        
        important during embryonic development
        
        Sheet of precursors (either glial or neurons) --> sheet of neurons interspersed between helper cells
        
        Delta bind to Notch cells
        
        undifferentiated cells with large Delta notch = neurons
        
        undifferentiated cells with large Notch protein = glial
        
        Plasmodesmata
        
        Bigger channels with smaller tunnels: viruses easily enter
        
        connects cytoplasm and ER
        
        Gap junctions
        
        tube like structure for smaller molecules
        
        coordinates cell through continuous tissue
      - autocrine signaling
        
        signaling cell = responding cell
        
        maintains developmental decision
        
        used by cancer cells
  - - - able to comm info through release of small peptide
      - binds to receptor --> bacterium expresses genes required for DNA uptake (antibiotic resistance)
      - Popn increases, concn of peptide increases
      - generates response
        
        Example: biofilms clump together
- - - - peptides (growth factors, insulin, cytokinesis)
      - small molecules
        
        non polar (lipids: hormones)
        
        polar (adrenaline)
      - gases (NO or ethylene)
  - - - ligand binds to G protein-coupled receptor
        
        Conformational change literally pulls in G-protein
        
        Conformational change on cytoplasmic side upon binding
      - evolutionary conserved
    - - Role in the cell
        
        involve changes in gene expression
        
        Responsible for embryonic development and cell division
        
        Example: Kit receptor kinase is prevalent in many organisms (responsible for production of pigments, feathers, etc)
      - Receptor kinases have extracellular portion
        
        Extracellular portion = receptor for ligand
        
        Intracellular portion = kinase
        
        partnering of two similar molecules in intracellular portion ligand binding --> dimerization --> conformational change --> activates cytoplasmic kinase
        
        cytoplasmic kinases phosphorylate each other at multiple sites
        
        provides places on receptor where other proteins bind and become active
    - - voltage-gated ion channels: opens in response to changes in voltage across membrane
      - ligand-gated ion channels: open when bound to ligand
    - - Polar molecules = receptors attached to transmembrane protein ---> undergoes conformational change --> signal transferred to internal cell
      - Nonpolar molecules = receptors located on inside of cell
        
        cortisone (inflammatory response)
        
        sex hormones
        
        glycocorticoids (raises blood pressure)
        
        ecdysone (insect molting)