3.D.3 Signal Transduction Signal transduction pathways link signal reception with cellular response.

Many chemical messengers cannot cross the plasma membrane.

Signal transduction is the process by which an extracellular signal is converted to an intracellular reponse.

Signaling begins with the recognition of a chemical messenger, a ligand, by a receptor protein.

A ligand can be: Ions Proteins (hormones) Neurotransmitters Steroids Many other types

Different receptors recognize different ligands in a specific one-to-one relationship.

When a ligand binds to a receptor, it causes the receptor protein’s shape to change (conformation change).

The conformation change of the receptor initiates transduction of the signal.

Ligand-gated Ion Channels Receptor Tyrosine Kinases Types of Receptors: G Protein Receptors Ligand-gated Ion Channels Receptor Tyrosine Kinases

G-protein linked receptors

The ligand binds to the receptor.

The receptor is attached to a G-protein, which is bound to a GDP molecule.

The binding of the ligand to the receptor causes a conformation change in the receptor. The GDP attached to the G-protein is replaced with a GTP.

The G-protein disassociates from the receptor.

The G-protein binds to and activates of adenylate cyclase, which in turn produces the second messenger cyclic AMP (cAMP).

The cAMP phosphorylates a protein kinase, which begins a phosphorylation cascade that amplifies the signal.

Ligand-gated Ion Channels: Model: the Sodium Channel

The ligand that binds to the ion-gated sodium channel is the neurotransmitter acetylcholine.

The sodium channel is closed when acetylcholine is not bound to the receptor.

The sodium channel opens when acetylcholine is bound the receptor site.

Sodium is then able to diffuse into the cell down its concentration gradient.

Receptor Tyrosine Kinases (RTK): Model: Growth Factor Hormone

Inactivate RTKs are disassociated.

When growth factor binds to neighboring RTKs, they combine to become a cross-linked dimer.

Cross-linking activates the tyrosine kinase activity Cross-linking activates the tyrosine kinase activity. Each RTK in the dimer phosphorylates multiple tyrosines on the other RTK. This process is called cross-phosphorylation.

RTKs activate relay proteins that are able to active multiple signal transduction pathways at once.

Signaling cascades often amplify the incoming signals, with the result of appropriate responses by the cell.

Second messengers are often essential to the function of the cascade.

Second messengers can include cyclic GMP, cyclic AMP, calcium ions (Ca2+), and inositol triphosphate (IP3)

A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol. Pathways leading to the release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as additional second messengers.

Many signal transduction pathways cause: Protein modifications such as methylation that change the signaling process and regulate cell processes. Phosphorylation cascades that amplify the signal.

An Example Signal Transduction Pathway

Learning Objectives: LO 3.36 The student is able to describe a model that expresses the key elements of signal transduction pathways by which a signal is converted to a cellular response. [See SP 1.5]

References: https://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter17/animation__membrane-bound_receptors_that_activate_g_proteins.html https://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter17/animation__second_messenger__camp.html http://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter2/animation__receptors_linked_to_a_channel_protein.html http://www.dnatube.com/video/539/Receptor-Tyrosine-Kinase-Activation-and-Signalling