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3 types of cell signaling
- Endocrine
- Synaptic
- Paracrine/autocrine
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Endocrine
- Via hormones
- Adrenaline, estradiol, testosterone
- Endocrine cell secrete hormone > release hormone into blood stream > bind to receptors on target cell
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Synaptic
- B/w 2 nerve cells or nerves and targets
- Usually at specialized parts of the cell
- Acetylcholine
- Release NT to in synaptic cleft
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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
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Contact dependent
- Extracellular signaling: membrane to membrane
- Have membrane bound ligand and receptor
- Notch, hedgehog
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3 requirements for animal signaling
- Multicellular tissues need to maintain proportions during development
- Replace missing cells
- Kill of excess cells
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Ligand-receptor interaction
- Highly specific
- Lead to formation of intracellular signaling complexes that modify or degrade pre-existing proteins
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Discovery of cell-cell signaling
- Hans Spemann - 80 years ago
- "Embryonic induction" - cells signaling other cells to change their fate
- Did the organizer experiment
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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
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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
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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
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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
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Cell-surface receptors
- Enzyme-linked
- Proteolysis-based
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Protein phosphorylation
- Strategy for transduction inside of cell
- Target amino acid residues for phosphorylation:
- Yeast, plant, animals - Serine and Threonine
- Animals - Tyrosine
- Bacteria - Histidine
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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
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Kit Mutation
- Heterozygous mutants result in deficit of pigment cell on the midline of mice and humans
- Example of conservation of developmental patterning
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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
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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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