Signal Transduction

Vocabulary flashcards covering essential terms from the lecture on signal transduction.

G Protein-Coupled Receptor (GPCR)

Seven-transmembrane receptor. Signal activates the receptor; ligand-bound GPCR replaces GDP with GTP, causing the a-subunit to dissociate. This triggers a secondary messenger (cAMP, DAG, Ca2+, IP3) to further transmit the signal, leading to cell changes.

Receptor Tyrosine Kinase (RTK)

Transmembrane protein that dimerizes and autophosphorylates tyrosine residues after ligand binding. The signal is relayed by activated signaling proteins

Protein Kinase A (PKA)

activated by cAMP; catalyzes the phosphorylation of Ser/ Tyr residues of target proteins, leading to cellular responses.

signal transduction general steps

1. signal (ligand) interacts with a receptor; 2. activated receptor interacts with cellular machinery to produce second signal or change in protein activity; 3. cellular activity changes

ligand-receptor specificity

achieved by precise complementarity between signal and receptor molecules, with binding through noncovalent forces

ligand-receptor sensitivity

results from high affinity of receptors for their ligand; dissociation constant (Kd) is low; receptor detects small concentrations of ligand

amplification

activated receptor catalyzes the activation of a second enzyme, and so on in signaling cascade

protein kinase

uses ATP to phosphorylate Ser, Tyr, or Thr

phosphatase

removes phosphate from target protein

B-adrenergic pathway

1. epinephrine binds; 2. allosteric change in hormone-receptor complex causes GDP to be replaced by GTP, activating Gsa; 3. activated Gsa dissociates, activating adenylate cyclase to produce cAMP, which then activates protein kinase A. This can lead to Ca2+ influx in the heart, or increased glucose availability in skeletal muscles

Her2/ Neu receptor

does not require a ligand, typically available in small amounts. when amplified, this can lead to unregulated cell growth and proliferation (i.e. breast cancer)

herceptin

blocks receptors and stops signal transduction

steroid hormones

enter directly into the cell, bind to receptors, and regulate gene expression

Hormone response elements (HREs)

specific regulatory sequences in DNA that interact with receptor proteins following hormone binding

PKA structure and mechanism

has 2 regulatory and 2 catalytic subunits; cAMP binds to regulatory subunits, causing dissociation of activated catalytic subunits, leading to changes in the metabolic pathways or gene expression; can phosphorylate CREB, which binds to CRE when activated, causing a change in gene expression

deactivation mechanisms

GPCR: GTP cleaved to GDP via a-subunit, which reassociates all subunits and returns GPCR into inactivated state; cAMP: can be broken by phosphodiesterase to AMP to reduce overactivation; CRK (G-protein receptor kinase): phosphorylates GPCR tail, causing it to bind to Arestin to prevent intracellular signaling; Gai: inhibits AC

insulin pathway

1. insulin phosphorylates IRS-1; 2. PI-3 kinase binds, causing conformational change of PI-3 and activates kinase enzymatic activity; 3. PIP-2 phosphorylates to PIP-3, which activates ATK; 4. ATK enters nucleus and changes gene expression, or impacts metabolic pathway

deactivation of RTKs

ligand unbinds and dimers go back to monomers (or in insulin, dimers move apart); phosphatase dephosphorylates and deactivates the C-termini tyrosine residues