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)

Growth Hormone

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)

Membrane

Hormone (H)

Receptor (R)

Extracellular

[R] + [H] [RH]

KD = [R] [H][RH]

Intracellular

[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

Let [R] + [RH] = RT

Then = [RH]RT

11+KD / [H]

And =

[RH]

[H]KD

RT -1

Fewer receptors means reduced sensitivity:

Suppose - cell has 10,000 receptors- KD = 10 –8 M = 10 nM- 1000 bound receptors generate desired response

Then based on [H] = RT - 1

KD

[RH]

[H] = 1.1 x 10-9 M

With RT = 1100, then [H] = 1.0 x 10-7 M

With RT = 2000, then [H] = 1.0 x 10-8 M