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Essential Biochemistry Third Edition Charlotte W. Pratt | Kathleen Cornely. Lecture Notes for Chapter 10 Signaling. KEY CONCEPTS: Section 10-1. Receptor-ligand binding is described in terms of a dissociation constant.

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Essential Biochemistry

Third Edition

Charlotte W. Pratt | Kathleen Cornely

Lecture Notes for

Chapter 10

Signaling


Key concepts section 10 1
KEY CONCEPTS: Section 10-1

  • Receptor-ligand binding is described in terms of a dissociation constant.

  • G protein-coupled receptors and receptor tyrosine kinases are the two major types of receptors that transduce extracellular signals to the cell interior.

  • Regulatory mechanisms limit the extent of signaling.



A ligand binds to a receptor with a characteristic affinity k d
A ligand binds to a receptor with a characteristic affinity (Kd).

Units:Molarity

  • Kd = [Ligand] when the receptor is half-saturated.

  • Low values of Kd indicate strong binding (high affinity).



A ligand that binds to a receptor and elicits a biological effect is an agonist
A ligand that binds to a receptor and elicits a biological effect is an agonist.

Antagonist of Adenosine Receptor – Caffeine binds but does NOT elicit a response

Natural agonist for Adenosine Receptor


Most signaling occurs through two types of receptors
Most signaling occurs through two types of receptors. effect is an agonist.

  • G proteins

  • Kinases


Most signaling occurs through two types of receptors1
Most signaling occurs through two types of receptors. effect is an agonist.

  • G proteins

  • Kinases


Key concepts section 10 2
KEY CONCEPTS: Section 10-2 effect is an agonist.

  • Ligand binding to a G protein-coupled receptor alters its conformation so that an intracellular G protein becomes activated.

  • The G protein stimulates adenylatecyclase to produce the second messenger cAMP, which activates protein kinase A.

  • G protein-dependent signaling is limited by several mechanisms.

  • The phosphoinositide signaling system activates a G protein, which leads to the production of lipid-derived second messengers and the activation of protein kinase C.

  • Cross-talk results when signaling pathways share components.


G protein receptors contain seven transmembrane helices
G protein receptors contain seven transmembrane helices. effect is an agonist.

Physiological ligands for the β-adrenergic receptor


Gpcrs bind to and activate a g protein
GPCRs bind to and activate a effect is an agonist.G protein.

Complex

Receptor

G Protein

G Protein with GDP (orange) bound


The g protein cycle
The G Protein Cycle effect is an agonist.

Signaling is limited by the GTPase activity of the α subunit



Camp activates protein kinase a
cAMP activates Protein Kinase A. effect is an agonist.

PKA

R = Regulatory subunit

C = Catalytic subunit

  • The level of cAMP determines the level of activity of PKA.


The structure of protein kinase a
The Structure of Protein Kinase A effect is an agonist.

Zoomed in view of active site





Calmodulin mediates some ca 2 signals
Calmodulin mediates some Ca messengers.2+ signals.

Ca2+

Calmodulin has an extended shape.

Calmodulin wraps around

its protein target!


Key concepts section 10 3
KEY CONCEPTS: Section 10-3 messengers.

  • Ligands such as insulin activate the tyrosine kinase activity of their receptors.

  • Receptor tyrosine kinases trigger cellular responses by phosphorylating target proteins and by activating Ras.



Insulin receptor tyrosine kinase undergoes autophosphorylation
Insulin receptor tyrosine kinase undergoes autophosphorylation.

Light blue = inactive receptor

Dark blue = activation loop

Light green = active receptor

Dark green = activation loop

  • A conformational change occurs to facilitate autophosphorylation.



Key concepts section 10 4
KEY CONCEPTS: Section 10-4 autophosphorylation.

  • Lipid hormones bind to intracellular receptors that regulate gene expression.

  • Eicosanoids are local mediators that act through G protein-coupled receptors.



Some receptors are transcription factors
Some receptors are transcription factors. autophosphorylation.

The Glucocorticoid Receptor-DNA Complex



Aspirin inhibits cyclooxygenase
Aspirin inhibits cyclooxygenase. molecules.

  • Prostaglandin synthesis is inhibited, thereby reducing pain.


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