Cell signaling pathways

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Author:
LT24
ID:
5388
Filename:
Cell signaling pathways
Updated:
2010-01-28 18:01:33
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cell Midterm 1
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Week #2
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  1. 3 types of cell signaling
    • Endocrine
    • Synaptic
    • Paracrine/autocrine
  2. Endocrine
    • Via hormones
    • Adrenaline, estradiol, testosterone
    • Endocrine cell secrete hormone > release hormone into blood stream > bind to receptors on target cell
  3. Synaptic
    • B/w 2 nerve cells or nerves and targets
    • Usually at specialized parts of the cell
    • Acetylcholine
    • Release NT to in synaptic cleft
  4. Paracrine
    • Local signaling over one or many cell diamters in a tissue/organ
    • Epidermal growth factor (EGF), Nitrous oxide (NO)
    • Ligand diffuse to nearby cells and bind to a receptor
  5. Contact dependent
    • Extracellular signaling: membrane to membrane
    • Have membrane bound ligand and receptor
    • Notch, hedgehog
  6. 3 requirements for animal signaling
    • Multicellular tissues need to maintain proportions during development
    • Replace missing cells
    • Kill of excess cells
  7. Ligand-receptor interaction
    • Highly specific
    • Lead to formation of intracellular signaling complexes that modify or degrade pre-existing proteins
  8. Discovery of cell-cell signaling
    • Hans Spemann - 80 years ago
    • "Embryonic induction" - cells signaling other cells to change their fate
    • Did the organizer experiment
  9. Organizer Experiment
    • Took tissue from frog egg and transplanted it into another frog egg
    • Took dorsal cells and transplanted it -> developed 2 dorsal sides
    • The transplanted cells signaled to adjacent cells that they are going to develop as dorsal cells
  10. Nuclear receptor superfamily
    • Steroid receptors
    • RXR heterodimers receptors
    • Dimeric orphan receptors
    • Monomeric orphan receptors
    • When hormone binds to receptor, the receptor signals transcription of certain genes
  11. Transmembrane signa transduction
    • Weak external signal can produce a large intracellular effect
    • Highly regulated
    • Almost always trigger negative feedback mechanisms
    • Signals are persmissive, not instructive
    • Cell already knows what its function is, it just needs the signal to do it
  12. Growth factors
    • Many signaling proteins discovered as "Growth factors"
    • Allow growth of cells
    • Wound cell culture -> add growth factors -> restoration of layer
    • Wound cell culture -> inhibit growth factor -> no restoration
  13. Cell-surface receptors
    • Enzyme-linked
    • Proteolysis-based
  14. Protein phosphorylation
    • Strategy for transduction inside of cell
    • Target amino acid residues for phosphorylation:
    • Yeast, plant, animals - Serine and Threonine
    • Animals - Tyrosine
    • Bacteria - Histidine
  15. Kit Receptor Tryrosine Kinase
    • Ligand bind to receptor -> receptor dimerizes -> cause cross phosphorylation of receptor
    • Adaptor protein activated -> phosphorylates Ras
    • Ras phosphorylates RAF
    • RAF -> MEK-P
    • MEK -> ERK
    • ERK modifies txn factors in nucleus by phosphorylation -> bind to DNA -> activate txn of melanoblast
  16. Kit Mutation
    • Heterozygous mutants result in deficit of pigment cell on the midline of mice and humans
    • Example of conservation of developmental patterning
  17. EFGR Pathway
    • Epidermal growth factor receptor
    • Ligand bind to receptor -> receptor dimerizes -> cause cross phosphorylation of receptor
    • GRB2 docks on Tyrosin-P sites
    • BRB2 -> Ras-P
    • Ras-P -> RAF
    • RAF-P -> MEK-P
    • MEK-P -> MAPK-P
    • MAPK modifies txn factors in nucleus by phosphorylation -> bind to DNA -> activate txn
    • Phosphate groups removed by phosphatase enzymes to start a new cyle
  18. Insulin RTK pathway
    • Defect leads to diseases such as diabetes
    • Reduced signaling = less glucose transport = higher glucose levels outside cells including in blood

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