Second Messenger, Catalytic, and Steroid Receptor Signaling

Vocabulary flashcards covering G protein-coupled receptor pathways, second messenger generation, catalytic receptor mechanisms, and steroid hormone signaling pathways.

Signal Transduction

The overall process by which an extracellular chemical signaling molecule (ligand) binds to its specific receptor, initiating a sequence of intracellular reactions that relay the signal and produce a biological response in the target cell.

G Protein-Linked Receptors

Transmembrane proteins containing seven membrane-spanning regions, an extracellular ligand-binding domain, and an intracellular domain that interacts with heterotrimeric G proteins to initiate signaling.

Heterotrimeric G Proteins

Intracellular membrane-associated G proteins composed of $\alpha$, $\beta$, and $\gamma$ subunits that are complexed together and bound to GDP in their inactive state.

$G_s$ Family

A family of heterotrimeric G proteins whose active $\alpha$ subunit ($G_{\alpha s}$) stimulates adenylyl cyclase activity, increasing intracellular cyclic AMP ($cAMP$) production.

$G_i$ Family

A family of heterotrimeric G proteins whose active $\alpha$ subunit ($G_{\alpha i}$) inhibits adenylyl cyclase activity, preventing the production of cyclic AMP ($cAMP$).

$G_q$ Family

A family of heterotrimeric G proteins whose active $\alpha$ subunit ($G_{\alpha q}$) activates phospholipase C, leading to the generation of second messengers $IP_3$, DAG, and $Ca^{2+}$.

Second Messengers

Intracellular signaling molecules generated in response to receptor activation that relay and amplify the original signal, regulating serine/threonine kinases to alter substrate activities.

Adenylyl Cyclase

A plasma membrane-bound enzyme regulated by G protein $\alpha$ subunits that catalyzes the conversion of ATP into the second messenger cyclic AMP ($cAMP$) and inorganic pyrophosphate ($PP_i$).

Protein Kinase A (PKA)

A $cAMP$-dependent serine/threonine kinase composed of regulatory and catalytic subunits; binding of $cAMP$ to the regulatory subunits releases active catalytic subunits that phosphorylate specific protein substrates.

cAMP Phosphodiesterase

An enzyme that hydrolyzes cyclic AMP ($cAMP$) to $5'\text{-AMP}$, terminating the intracellular effects of increased $cAMP$ once the extracellular signal is removed.

Cholera Toxin

A toxin produced by Vibrio cholerae that modifies the $\alpha$ subunit of $G_s$ in intestinal epithelial cells, preventing GTP cleavage to GDP and causing continuous overproduction of $cAMP$, diarrhea, and dehydration.

Pertussis Toxin

A toxin produced by Bordetella pertussis that inhibits the $\alpha$ subunit of $G_i$ in the respiratory tract, preventing adenylyl cyclase inhibition and leading to excess $cAMP$ production.

Phospholipase C

A membrane-bound enzyme activated by $G_{\alpha q}$ that cleaves the membrane lipid phosphatidylinositol 4,5-bisphosphate ($PIP_2$) into inositol 1,4,5-trisphosphate ($IP_3$) and diacylglycerol (DAG).

Inositol 1,4,5-Trisphosphate ($IP_3$)

A soluble second messenger generated by phospholipase C that binds to specific receptors on the endoplasmic reticulum, triggering the rapid release of stored calcium ions ($Ca^{2+}$) into the cytosol.

Diacylglycerol (DAG)

A membrane-anchored second messenger generated by phospholipase C cleavage of $PIP_2$ that, together with $Ca^{2+}$, activates Protein Kinase C (PKC).

Protein Kinase C (PKC)

A serine/threonine kinase anchored to the membrane that is activated by diacylglycerol (DAG) and $Ca^{2+}$ to phosphorylate cellular proteins that mediate biological responses.

Calmodulin

An intracellular calcium-binding protein that binds four $Ca^{2+}$ ions during cytosolic calcium elevations to form an active calmodulin-$Ca^{2+}$ complex that regulates calcium-dependent enzymes.

Catalytic Receptors

Transmembrane receptors that signal via tyrosine phosphorylation of intracellular substrates, possessing intrinsic protein tyrosine kinase activity or associating non-covalently with non-receptor tyrosine kinases.

Adaptor Proteins

Intracellular signaling molecules containing conserved SH2 and SH3 domains that dock at phosphotyrosine residues on activated receptor tails to assemble signaling complexes without possessing intrinsic enzyme activity.

Ras

A small monomeric GTP-binding G protein anchored to the inner plasma membrane that acts as a molecular switch, exchanging GDP for GTP via GEF (SOS) to initiate the MAP kinase cascade.

MAP Kinase Cascade

A serine/threonine phosphorylation cascade triggered by active Ras-GTP (Raf $\rightarrow$ MEK $\rightarrow$ ERK/MAPK) that terminates with MAPK translocating to the nucleus to phosphorylate transcription factors.

STATs

Signal Transducers and Activators of Transcription; SH2-containing cytoplasmic proteins that bind phosphotyrosines on activated receptors, become tyrosine-phosphorylated, form dimers, and translocate to the nucleus to induce gene transcription.

PI3 Kinase Pathway

A catalytic receptor signaling pathway where activated PI3 kinase phosphorylates membrane $PIP_2$ to convert it into $PIP_3$, providing docking sites to recruit and activate Akt.

Akt

A serine/threonine kinase recruited to the membrane by $PIP_3$ and activated by phosphorylation, which subsequently phosphorylates Bad to promote cell survival.

PTEN

A lipid phosphatase that dephosphorylates inositol phospholipids like $PIP_3$ back to $PIP_2$, thereby inorganically inactivating PI3 kinase pathway signaling.

Non-Receptor Tyrosine Kinases

Cytoplasmic tyrosine kinases (such as the Src and Janus kinase families) that non-covalently associate with the cytoplasmic tails of receptors lacking intrinsic kinase activity to phosphorylate tyrosine residues upon ligand binding.

Insulin Receptor

A pre-formed tetrameric receptor ($\alpha_2\beta_2$) joined by disulfide bonds that possesses intrinsic tyrosine kinase activity in its intracellular $\beta$ subunit domains, auto-phosphorylating upon insulin binding without requiring chain dimerization.

Insulin Receptor Substrates (IRS)

Cytoplasmic target proteins (IRS-1, IRS-2, IRS-3, IRS-4) phosphorylated on tyrosine residues by the activated insulin receptor kinase to recruit signaling molecules like Ras, STATs, and PI3 kinase.

Nuclear-Initiated Steroid Signaling (NISS)

Classical steroid hormone signaling where lipophilic steroids cross the plasma membrane to bind intracellular receptors, converting them into active ligand-activated transcription factors that bind hormone response elements (HREs) on DNA.

Membrane-Initiated Steroid Signaling (MISS)

Rapid steroid signaling mechanism mediated by steroid receptors localized to plasma membrane caveolae that associate with signaling complexes to trigger rapid kinase cascades and target protein modifications within seconds to minutes.

Caveolae

Specialized flask-like invaginations of the plasma membrane where membrane-associated steroid receptors dock alongside signaling proteins including G proteins, Src, Ras, and growth factor receptors.

Steroid Hormone Receptor Structure

The modular functional architecture of intracellular steroid receptors consisting of an $NH_2\text{-terminal}$ gene regulatory domain, a DNA-binding domain, a flexible hinge region, and a $COOH\text{-terminal}$ hormone-binding domain.