Signal Transduction

• Intracellular receptors


  Receptors found on the inside of the cell, usually in the cytoplasm or nucleus
• Intracellular receptors generally receive small hydrophobic ligands that are able to get through the membrane
• When activated, intracellular receptors bind to genes to alter their transcription
• Cell-surface receptors


  Membrane-anchored proteins that typically have a ligand-binding domain on the outside, a hydrophobic domain through the phospholipid bilayer, and an intracellular domain
• Ligand-gated ion channels


  Cell-surface receptors that open into ion channels when activated (or vv), letting ions pass through without having to deal with the hydrophobic core of the membrane
• G protein coupled receptors


  GPCRs
• Heterotrimetric G proteins


  G proteins made up of 3 subunits that associate with GPCRs
• GPCRs


  Receptors that send off G protein alpha subunits by switchig GDP for GDP when activated by a ligand, which go on to do other things within the cell by triggering other receptors or enzymes
• G proteins all bind with GTP which they hydrolyze into GDP so they can break off and do things when activated
• Enzyme linked receptors


  Cell-surface receptors with intracellular domains that are associated with an enzyme
• Receptor tyrosine kinases (RTKs)


  Class of enzyme-linked receptors that transfer phosphate specifically to the amino acid tyrosine that can bind to growth factors
• Kinase


  Enzyme that transfers a phosphate group to a protein or other target
• RTKs work by dimerizing when activated, then phophorylating the other's tyrosines. Once this happens, they go on to affect other cell systems
• Steroid hormones


  Small hydrophobic ligands that can pass through the phospholipid membrane like estradiol (estrogen) and testosterone
• Nitrous oxide


  Gas that acts as a ligand that activates signaling pathways in smooth muscles to relax them and make blood vessels expand (viagra)
• Peptides and hydrophilic molecules bind to the outside of the cell, including amino acids and neurotransmitters
• Intracellular signal transduction pathways


  Chain of molecules and relay signals that communicate within a cell
• Upstream


  Things that happen earlier in the signal transduction pathway
• Downstream


  Things that happen later in the signal transduction pathway
• Phosphate groups have to be added to hydroxyl groups, so they typically bind to tyrosine, threonine, or serine
• Phosphatases


  Enzymes which remove a phosphate group from their targets
• Mitogen


  Signal that causes cells to undergo mitosis
• MAPK cascade

  
• Steps of MAPK cascade:

  • GF binds to receptors which pair up and act as kinases for each other
  • Triggers events that activate kinase Raf
  • Active Raf phosphorylates MEK, which does the same for the ERKs
  • ERKs phosphorylate a variety of targets which promote cell growth and division
• Second messengers


  Small non protein molecules that pass along the signal given by the ligand binding to its receptor (the first messenger)
• Second messengers


  Includes Ca2+ ions, cAMP, and inositol phosphate
• Calcium ions are in low concentration in the cell because of pumps, but some receptors trigger channels to open that let them in. There are many cell structures with their receptors whose activities change when bound
• Cyclic adenosine monophosphate


  cAMP
• Adenylyl cyclase


  Enzyme that converts ATP into cAMP by removing two phosphates and linking the remaining one back around to form a ring shape
• Protein kinase A


  Enzyme activated by cAMP that phosphorylates its targets, which depend on the context and so its function is versatile
• Phosphodiesterase


  Enzyme which turns off cAMP signaling by breaking the ring and turning it into boring adenosine monophosphate (AMP)
• Phosphatidylinositols


  Membrane phospholipids that can be phosphorylated, which then snips them in half to create two separate molecules that both act as second messengers (like PIP2 which can be turned into DAG and IP3)
• When PIP2 is phosphorylated, it turns into 2 smaller molecules that become second messengers. DAG stays in the membrane and activates protein kinase C, while IP3 diffuses into the cytoplasm and binds to Ca2+ channels, opening them and causing them to come in
• c-Myc


  Transcription factor targeted by growth factor that can lead to cancer if it's too good at promoting cell growth
• MKN1


  Translational regulator targeted by growth factor that increases mRNA translation, especially on certain ones that fold over on themselves to make hairpin structures, some of which are important for signaling cell growth and division
• Glycogen phosphorylase


  Enzyme that breaks down glycogen into glucose downstream of epinephrine binding to a receptor
• When epinephrine activates a reaction in a cell, it inhibits glycogen from being formed and starts breaking it down into glucose, giving it a surge of energy
• Apoptosis


  The controlled death of a cell ensuring that it is destroyed safely without contents escaping to cause more hard. Triggered when bad DNA is sensed, or when they stop getting signals from their ECM, signaling that it's strayed too far. System is broken when cancer cells metastasize