1' Categorize chemical signals in terms of the proximity of the communicating cells'

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1. Categorize chemical signals in terms of the
proximity of the communicating cells.

• Local Regulators
• Paracrine signaling ? one cell secretes the
  signal into extracellular fluid and acts on
  another cell
• Synaptic signaling ? a nerve cell releases a
  signal into a synapse, such as another nerve cell
  or muscle cell

• Hormones
• Communicates signals between cells far apart
  examples
• Plants ethylene gas which promotes ripening
• Animals insulin, a protein which regulates
  blood glucose levels ?

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2. Overview the basic elements of a signaling
system of a target cell.

• 1. Reception ? signal binds to a specific
  cellular protein called a receptor, often at the
  cells surface
• 2.Transduction ? the binding changes the
  receptors conformation which initiates a process
  of converting the signal into a specific cellular
  response (which may have 1 or more steps)
• 3. Cellular response ? can be almost any cellular
  activity, such as activation of an enzyme or
  altered gene expression ?

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3. Describe the nature of a ligand-receptor
interaction and state how such interactions
initiate a signal transduction system.

• Ligand ? term for a small molecule that binds to
  another larger molecule
• The signal molecule is complementary to a
  specific region of the receptor protein
• ? the alteration in receptor conformation or
  shape can lead to the activation of the receptor
  which enables it to interact with other cellular
  molecules ?

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4. Compare and contrast G-protein-linked
receptors, tyrosine-kinase receptors, and
ligand-gated ion channels.

• G-protein linked ? single polypeptide chain
  threaded over membrane
• - interacts with a variety of proteins
• - hosts metabolic and developmental processes
• Tyrosine-kinase ? characterized by an
  extracellular ligand-binding domain and enzyme
  activity
• - ligand binding causes aggregation of 2
  receptor units which activates the kinase
  activity
• Ion channels ? protein pores in the membrane that
  open or close in response to ligand binding,
  allowing or blocking the flow of specific ions ?

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5. Describe how phosphorylation propagates signal
information.

• Some phosphorylation results in activation of the
  target protein (increasing catalytic activity)
• Some result in inactivation
• Protein kinases act on other proteins (sometimes
  enzymes) and attach the phosphate group to serine
  or threonine residues
• Used in signal paths in the cytoplasm of the cell
  ?

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6. Describe how cAMP (cyclic AMP) is formed and
how it propagates signal information.

• Ligand binds to receptor
• Receptor conformation changes G-protein complex
  is activated
• Active G-protein activates the enzyme adenylyl
  cyclase which is associated with the cytoplasmic
  side of the plasma membrane
• Adenylyl cyclase converts ATP to cAMP
• cAMP binds to and activates a cytoplasmic enzyme
  protein kinase A
• Protein kinase A propagates the message by
  phosphorylating various other proteins that lead
  to the cellular response ?

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7. Describe how the cytoplasmic concentration of
Ca 2 can be altered and how this increased pool
of Ca 2 is involved with signal transduction.

• Altered in two ways
• 1. Ligand binding to a Ca2 ion-gated channel
• 2. Activation of the inositol triphosphate (IP3)
  signaling pathway
• - ligand binds, conformation change
• - IP3 is created and binds to Ca2 ion-gated
  channels ?

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Continued

• Ca2 affects the signal transduction
• 1. Directly ? affects the activity or function
  of target proteins
• 2. Indirectly ? binds to a relay protein which
  in turn alters the activity of enzymes ?

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8. Describe how the signal information is
transduced into cellular responses in the
cytoplasm and in the nucleus.

• Cytoplasm ? affect on the function or activity of
  the proteins, including
• - rearrangement of the cytoskeleton
• - open/close of an ion channel
• - key points in metabolic pathways
• Nucleus ? affect on synthesis of new proteins by
  turning on/off genes
• - transcription/translation
• - gene expression ?

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9. Describe how signal amplification is
accomplished in target cells.

• The making of second messengers like cAMP
  provides some amplification
• - this is increased when it is linked to a
  phosphorylation cascade
• - ex few epinephrine molecules are needed to
  result in millions of glucose molecules released
  from glycogen in the liver ?

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10. Describe how target cells discriminate among
signals and how the same signal can elicit
multiple cellular responses.

• Discriminate ? like the enzyme, it is specific to
  certain cells and receptors
• Multiple responses ? depending on the cell it
  binds to, the responses can vary hugely
• ex epinephrine on liver vs cardiac
• - liver ? induces breakdown of glycogen
• - heart ? stimulates contraction ?