A5 other signaling pathways

What is a receptor tyrosine kinase (RTK)?

A receptor with intrinsic kinase activity that phosphorylates tyrosine residues on target proteins.

What domains are involved in RTK signaling?

• Extracellular domain (ligand binding, often α subunit)

• Transmembrane segment

  • Intracellular kinase domain (β subunit, catalytic activity)

What is autophosphorylation and why is it important?

Each RTK monomer phosphorylates its partner on tyrosine residues, activating catalytic activity and creating docking sites for signaling proteins.

What is IRS1 and its role in insulin signaling?

Insulin receptor substrate 1; becomes phosphorylated and nucleates complexes to transmit the signal downstream.

What is an SH2 domain?

A domain in proteins that binds phosphorylated tyrosine residues, allowing recruitment to activated receptors.

What is the role of Grb2 in insulin signaling?

An adaptor protein with SH2 domains that links IRS1 to SOS.

What is SOS and its role?

A guanine exchange factor (GEF) that activates Ras by replacing GDP with GTP.

What is Ras and how is it activated?

A small GTP-binding protein activated by SOS; active Ras triggers the MAPK cascade.

Describe the MAPK cascade downstream of Ras.

: Ras → Raf → MEK → ERK → ERK enters nucleus to activate transcription factors for gene expression.

How does insulin signaling affect GLUT-4 transporters?

PI3K pathway phosphorylates PIP2 to PIP3 → recruits proteins that cause GLUT-4 vesicles to translocate to the membrane → increases glucose uptake.

What is the resting membrane potential and what establishes it?

About –70 mV; established primarily by the Na+/K+ pump and K+ leak channels.

What happens during depolarization?

: Voltage-gated Na+ channels open → Na+ rushes in → inside becomes less negative.

What happens during repolarization?

Voltage-gated K+ channels open → K+ flows out → membrane potential returns negative.

What is the refractory period?

Time after an action potential when Na+ channels are inactivated and cannot reopen immediately.

What is an action potential?

A wave of depolarization (Na+ influx) followed by repolarization (K+ efflux) that travels along a neuron.

What happens at the synapse?

Action potential arrives → Ca²⁺ channels open → neurotransmitters released → bind to ligand-gated channels on postsynaptic cell → depolarization continues.

How do steroid hormones reach their receptors?

Carried in blood by binding proteins → diffuse through membrane → bind receptor in cytosol or nucleus.

What are the states of the glucose transporter?

• T1: Glucose binding site is exposed on the outer membrane.

  • T2: Glucose binding site is exposed on the inner membrane.

What are the steps of the SERCA pump cycle?

• Ca²⁺ and ATP bind to the N domain → N domain moves toward P domain.

• Phosphoryl group transferred to Asp in P domain.

• Conformational change releases Ca²⁺ into the lumen.

• A domain moves and releases ADP.

• P domain is dephosphorylated.

• A domain released.

  • Pump resets back to E1 to restart the cycle.

What are the steps of GPCR signaling with epinephrine?

• Epinephrine binds to receptor.

• G-protein α-subunit releases GDP, binds GTP.

• GTP-bound α-subunit activates adenyl cyclase.

• Adenyl cyclase produces cAMP.

• cAMP activates PKA.

• PKA phosphorylates target molecules.

  • cAMP is degraded.

What are the steps of RTK (insulin receptor) signaling?

• Insulin binds receptor → autophosphorylation on tyrosine residues (insulin already a dimer, no need to dimerize receptor).

• IRS1 phosphorylated at 3 tyrosines.

• SH2 domain of Grb2 binds phosphate → SOS binds to Grb2 → Ras releases GDP and binds GTP.

• Ras activates Raf1.

• ERK is phosphorylated → translocates to nucleus.

• ERK acts as a transcription factor.

• Gene transcription is activated.