Ch_15_Signalling - CELL SIGNALING Modes: Endocrine-...

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CELL SIGNALING Modes: Endocrine- signaling molecules carried thru circulation to affect distant targets Paracrine- molecules act on neighboring target cells Juxtacrine- molecule acts on cell right next to the cell, cell/cell contact? Autocrine- signaling molec acts on the cell that secreted it. HYDROPHOBIC LIGANDS Steroid hormones, Thyroid hormone, Vit D3, Retinoids: o Receptors are inside the cell o Steroids diffuse across the PM to bind to receptors o Steroids synthesized from cholesterol o Bind to receptors that are transcription factors, called the nuclear receptor superfamily. Activate/repress gene transcription o Estrogen Binds receptor in cytosol, which was originally inactive when bound to Hsp90. When estrogen-bound, receptor released from Hsp90, dimerizes, and binds DNA, associates with coactivators, increases transcription. o Thyroid Hormone When unbound to ligand, receptor bound to corepressors. When thyroid hormone binds, receptor bound to coactivators instead and transcription can initiate. Nitric Oxide (and carbon monoxide) o Major paracrine signaling molecule o Diffuses directly across plasma membrane o Synthesized from arginine by NO synthase o Activates guanylyl cyclase, stimulates synthesis of cGMP from GTP. o Important in dilation of blood vessels cGMP activates PKG, which phosphorylates enzymes Neurotransmitters o Hydrophilic molecules Ach, Dopa, Epi, GABA, serotonin, histamine, glutamate, glycine o Released by arrival of action potentials at terminus of neuron o Diffuse across synaptic cleft and bind to receptors on target cell surface Cannot cross PM b/c hydrophilic o Ligand binding induces opening of ion channels or activates Gproteins. Peptide hormones and Growth Factors
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o Peptide Hormones: Insulin, glucagons, growth hormone, FSH, prolactin, etc o Neuropeptide hormones: Enkephalins and endorphins function as both NT and NP. o Growth Factors Control cell growth and differentiation NGF, EGF, PDGF, etc Cytokines o These all act by binding to surface receptors Eicosanoids o Lipids that serve as signaling molecules, bind to cell surface receptors o Prostaglandins, prostacyclin, thromboxanes, and leukotrienes o Act locally in autocrine or paracrine signaling pathways o Synthesized from arachidonic acid. o
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Ch_15_Signalling - CELL SIGNALING Modes: Endocrine-...

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