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Cell to Cell Communication. Signal Transduction Converting an extracellular signal to an intracellular response Primary Messengers Hormones, neurotransmitters, growth factors, cytokines, prostaglandins, etc. Messenger = Ligand (Binds to receptor with great specificity) Secondary Messengers
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Cell to Cell Communication • Signal Transduction • Converting an extracellular signal to an intracellular response • Primary Messengers • Hormones, neurotransmitters, growth factors, cytokines, prostaglandins, etc. • Messenger = Ligand (Binds to receptor with great specificity) • Secondary Messengers • cAMP, Phosphoinositides, Ca2+
Why Use Hormone Signaling? • General systemic responses • Any cells that possess receptors • Longer acting, slower developing responses • Cause changes in cell growth, differentiation, function • Exert varied responses in different cells/tissues • Cells can have different numbers of receptors or develop different responses with same receptors • Can integrate different messenger inputs • Control inputs can be prioritized (e.g., local control can be modulated or overridden)
Control of Chemical Signals • Short-term • Release, uptake and clearance • Longer-term • Up or down regulation of number of receptors (highly variable from ~2,000 to ~100,000)
Extracellular Hormone (H) Membrane Receptor (R) Intracellular [R] + [H] [RH] [R] [H] KD = [RH] [H] = KD when [R] = [RH]
What does Kd mean? • For insulin, Kd is 2(10-8)M • M= molar = moles/liter = concentration of substance • Insulin has a molecular weight of 5,808 g/mole • Thus, concentration of insulin when half of receptors are bound is equal to 2(10-8)M x 5,808 g/mole = 0.00012 g/l or 0.12 μg/ml • Blood contains ~10,000 μg/ml of total protein • Insulin signaling occurs in the presence of ~100,000 excess protein (background “noise”) • Erythropoietin has a Kd of 10-10M (0.003 μg/ml) • Signaling occurs in the presence of >3,000,000 background
[RH] 1 Then = RT 1+KD / [H] KD [H] And = RT -1 [RH] Let [R] + [RH] = RT
KD Then based on [H] = RT - 1 [RH] Fewer receptors means reduced sensitivity: Suppose - cell has 10,000 receptors - KD = 10 –8 M = 10 nM - 1000 bound receptors generate desired response [H] = 1.1 x 10-9 M With RT = 2000, then [H] = 1.0 x 10-8 M With RT = 1100, then [H] = 1.0 x 10-7 M