Cell Signaling

• Endocrine signaling


  • Long range, systemic signaling via hormones transported through the bloodstream (animals) or sap (plants)
  • Hormones made in endocrine cells
  • Examples: insulin, adrenaline, melatonin, estrogen & testosterone
• Paracrine signaling


  • Signaling by proteins secreted into extracellular space
  • Proteins produced by ER and released from plasma membrane
  • Can be short (cell to cell) or long range (across tissue)
  • Moved by diffusion
  • Examples: developing embryo, wound healing, cancer
• Synaptic signaling


  • From neurons to other cells
  • Electrical signaling (action potential) results in release of neurotransmitters stored in vesicles at the synapse
  • Very local signaling
  • Neurotransmitters: dopamine, glutamine, GABA
• Contact dependent (juxtacrine) signaling


  • Direct, physical contact between cells
  • Signal never leaves the signaling cell
  • Example: immune system, embryo development
• Intracellular receptors


  For very small or hydrophobic signals that can cross membrane, bind receptors inside cell or directly to enzymes
• Fast vs slow response to signaling

  Depends on whether transcription and translation are needed for the response
• Signaling by protein phosphorylation

  • Phosphorylation usually activates an enzyme
  • Protein kinases (enzymes) phosphorylate target proteins by transferring phosphate group from ATP to specific protein
• Steroid hormones

  • type of intracellular receptor
  • they can cross plasma membrane and bind directly to receptors in cytoplasm
  • the receptors relocate to the nucleus and act as transcription regulators
  • Ex. cortisol, estradiol, testosterone, and thyroxine
• Ion channel coupled receptors

  • primary signal receptor in neurons
  • convert chemical signal (signaling molecule) back into electrical signal (voltage)
  • Ex. Glutamate
• cAMP

  • cAMP --> AMP is blocked by caffeine, which makes us jittery and alert
  • GPCR rapidly generate cAMP
  • cAMP can bind to and activate PKA, which in turn, phosphorylate other proteins
• receptor tyrosine kinase (RTK)

  • signal binding causes receptor dimerization and auto-phosphorylation
  • many cancer feature misregulation of RTK
• Nearly all RTK activate Ras (membrane bound GTPase protein)

  • RTK phosphorylation leads to Ras binding to GTP, making Ras-GTP (active) transmit signaling into cytoplasm
  • Ras triggers 3 rounds of amplification, which phosphorylation of effector proteins that can change gene expression or protein activity
• Delta-Notch Signaling


  delta signal on signaling cell binds to notch receptor, causing notch to cleave into 2 proteins, with intracellular part traveling to nucleus as transcription regulator