Cell Signaling

Vocabulary practice flashcards covering cell communication, signal transduction pathways, GPCRs, second messengers, RTKs, Ras, and intracellular receptors from Chapter 16 lecture slides.

Signal Transduction

The biochemical process by which an extracellular impulse or stimulus is converted from one physical or chemical form to another, producing intracellular signaling molecules that alter cell behavior.

Endocrine Signaling

A long-range mode of cell communication in which specialized endocrine cells secrete hormones into the bloodstream, distributing them widely throughout the body to act on distant target cells.

Paracrine Signaling

A local form of cell communication where signaling cells secrete local mediators into the extracellular fluid to act on neighboring target cells located short distances away.

Synaptic Signaling

A rapid, specialized long-distance communication mechanism in which an electrical impulse travels along a nerve cell axon, triggering the release of neurotransmitters across a synaptic cleft ($<100\,\text{nm}$) to stimulate a postsynaptic target cell.

Contact-Dependent Signaling

A mode of intercellular communication requiring direct physical contact between cells, where a membrane-bound signal molecule on the signaling cell binds to a receptor embedded in the plasma membrane of an adjacent target cell without any secreted molecule.

Yeast Mating Factors

Peptide signaling molecules secreted by haploid yeast cells (mating type $\mathbf{a}$ secretes $\mathbf{a}$ factor; mating type $\alpha$ secretes $\alpha$ factor) that bind reciprocal cell-surface receptors, inducing cell changes that lead to cell fusion and the formation of a new diploid $\mathbf{a}/\alpha$ cell.

Lateral Inhibition

A contact-dependent process mediated by Delta signal proteins and Notch receptors where a developing cell (such as a neural precursor) inhibits its immediate neighboring epithelial cells from adopting the same specialized developmental fate.

Fast vs. Slow Signaling Responses

A temporal distinction where fast responses ($<\text{sec to mins}$) occur through direct changes in existing protein function and cytoplasmic machinery (e.g., cell movement, secretion), whereas slow responses ($\text{mins to hrs}$) require changes in gene transcription and new protein synthesis (e.g., cell differentiation, cell growth and division).

Effector Proteins

Intracellular proteins at the end of a signaling pathway that directly alter cell behavior when activated, including metabolic enzymes (altering metabolism), cytoskeletal proteins (altering cell shape or movement), and transcription regulators (altering gene expression).

Signal Amplification

The multiplication of an intracellular signal during transduction, allowing a small number of extracellular signal molecules to produce a massive intracellular physiological response through sequential enzymatic cascades.

Positive Feedback

A signaling regulatory mechanism in which a downstream component acts back on an upstream activator to enhance pathway activity, generating all-or-none, explosive biological responses.

Negative Feedback

A signaling regulatory mechanism in which a downstream product inhibits an upstream component that activated it, generating self-limiting, oscillating biological responses.

Protein Kinase

An intracellular molecular switch enzyme that covalently attaches a phosphate group from $\text{ATP}$ to specific amino acid side chains (such as serine/threonine or tyrosine) on a target protein, typically switching it from an inactive to an active state.

Protein Phosphatase

An enzyme that removes a phosphate group from a phosphorylated target protein via hydrolysis, releasing inorganic phosphate ($\text{P}_i$) and typically resetting the molecular switch to its inactive state.

Guanine Nucleotide Exchange Factor (GEF)

A regulatory protein that activates GTP-binding proteins (such as monomeric GTPases) by stimulating the release of tightly bound $\text{GDP}$, allowing abundant cellular $\text{GTP}$ to bind.

GTPase-Activating Protein (GAP)

A regulatory protein that inactivates GTP-binding proteins by stimulating their intrinsic rate of $\text{GTP}$ hydrolysis to $\text{GDP}$ and inorganic phosphate ($\text{P}_i$).

Ion-Channel-Coupled Receptor

A cell-surface transmitter-gated ion channel that opens or closes upon binding a specific extracellular neurotransmitter, permitting the flow of specific ions across the plasma membrane and altering membrane potential.

G-Protein-Coupled Receptor (GPCR)

The largest and most diverse eukaryotic cell-surface receptor family, characterized by a single polypeptide chain with seven transmembrane-spanning $\alpha$ helices that couples extracellular ligand binding to the activation of intracellular heterotrimeric G proteins.

Heterotrimeric G Protein

A membrane-associated molecular switch complex consisting of three protein subunits ($\alpha$, $\beta$, and $\gamma$); the $\alpha$ and $\gamma$ subunits are lipid-tethered to the plasma membrane, and ligand-bound GPCR triggers the $\text{G}\alpha$ subunit to exchange $\text{GDP}$ for $\text{GTP}$, dissociating into an active $\alpha$ subunit and an active $\beta\gamma$ complex.

$\text{G}_i$ Protein

An inhibitory G protein that regulates ion channels and enzymes; in heart pacemaker cells, acetylcholine binding leads to active $\beta\gamma$ subunits opening closed $K^+$ channels, increasing membrane permeability to $K^+$ and slowing the heart rate.

Cyclic AMP (cAMP)

A key water-soluble intracellular second messenger synthesized from $\text{ATP}$ by adenylyl cyclase and degraded into $\text{AMP}$ by cyclic AMP phosphodiesterase.

Cyclic AMP Phosphodiesterase (PDE)

The enzyme responsible for hydrolyzing active cyclic $\text{AMP}$ ($\text{cAMP}$) into inactive $\text{AMP}$, terminating $\text{cAMP}$-mediated intracellular signaling; it is inhibited by caffeine in the nervous system.

Protein Kinase A (PKA)

A cAMP-dependent serine/threonine protein kinase activated when cyclic $\text{AMP}$ binds its regulatory subunits; active PKA phosphorylates specific metabolic enzymes (such as phosphorylase kinase) or migrates through nuclear pores to phosphorylate gene transcription regulators.

Cholera Toxin

A bacterial toxin secreted by Vibrio cholerae that catalyzes the ADP-ribosylation of the $\text{G}_s\alpha$ subunit, abolishing its intrinsic GTPase activity and locking it in an active state, resulting in continuous adenylyl cyclase activation, elevated $\text{cAMP}$, constitutive CFTR activation, and massive intestinal water efflux ($2\,\text{L/hr}$).

Phospholipase C (PLC)

A membrane-bound enzyme activated by $\text{G}_q$ proteins that cleaves inositol phospholipids situated in the cytosolic leaflet of the plasma membrane into two distinct second messengers: diacylglycerol (DAG) and inositol 1,4,5-trisphosphate ($\text{IP}_3$).

Inositol 1,4,5-Trisphosphate ($\text{IP}_3$)

A water-soluble second messenger generated by phospholipase C that rapidly diffuses through the cytosol and binds to ligand-gated $Ca^{2+}$ channels in the endoplasmic reticulum membrane, releasing sequestered $Ca^{2+}$ into the cytosol.

Diacylglycerol (DAG)

A hydrophobic lipid second messenger produced by phospholipase C cleavage that remains embedded within the plasma membrane, where it acts together with cytosolic $Ca^{2+}$ to recruit and activate Protein Kinase C (PKC).

Protein Kinase C (PKC)

A serine/threonine kinase that is recruited from the cytosol to the plasma membrane and activated by membrane-bound diacylglycerol (DAG) and elevated $Ca^{2+}$, subsequently phosphorylating intracellular target proteins to propagate signals.

Calmodulin

A ubiquitous cytosolic eukaryotic $Ca^{2+}$-binding protein containing two globular ends connected by a long $\alpha$ helix, with each globular end possessing two $Ca^{2+}$-binding sites (four sites total); binding of $Ca^{2+}$ induces a conformational change that wraps around target proteins like CaM-kinases.

CaM-Kinase

A $Ca^{2+}$/calmodulin-dependent protein kinase activated by binding the $Ca^{2+}$-calmodulin complex, prominently involved in mediating processes of learning and memory in the mammalian brain.

Nitric Oxide (NO)

A dissolved, membrane-permeable gas produced by NO synthase (NOS) from arginine in vascular endothelial cells that diffuses into adjacent smooth muscle cells to activate guanylyl cyclase, converting $\text{GTP}$ to $\text{cGMP}$ and triggering rapid smooth muscle relaxation and blood vessel dilation.

Transducin

A trimeric G protein ($\text{G}_t$) in vertebrate retinal rod photoreceptor cells activated by light-stimulated rhodopsin; its active $\alpha$ subunit stimulates cGMP phosphodiesterase (PDE), which hydrolyzes $\text{cGMP}$, causing plasma membrane cation channels to close and the cell to hyperpolarize.

Receptor Tyrosine Kinase (RTK)

An enzyme-coupled cell-surface receptor spanning the plasma membrane with a single transmembrane segment; extracellular signal binding induces receptor dimerization, stimulating intrinsic kinase domains to phosphorylate specific intracellular tyrosine residues that serve as docking sites for downstream signaling proteins.

Protein Tyrosine Phosphatase (PTP)

An enzyme that terminates or modulates signaling initiated by ligand-activated RTKs by dephosphorylating tyrosine residues on active receptors and their associated intracellular signaling complexes.

Ras Protein

A small monomeric GTP-binding protein tethered to the cytoplasmic face of the plasma membrane by a lipid tail that acts as a molecular switch downstream of RTKs, transitioning to an active $\text{GTP}$-bound state via Ras-GEF to stimulate cell proliferation and growth.

MAP-Kinase Signaling Module

A conserved three-kinase intracellular phosphorylation cascade consisting of MAP kinase kinase kinase (Raf), MAP kinase kinase (Mek), and MAP kinase (Erk) that relays mitogenic signals from active Ras to phosphorylate cytosolic proteins and nuclear transcription regulators.

Ras Oncogenes

Mutated forms of RAS genes that disrupt the protein's intrinsic GTPase activity, locking Ras permanently in an active $\text{GTP}$-bound state and driving uncontrolled cell growth; mutated in more than $30\%$ of all human cancers, including $95\%$ of pancreatic cancers (KRAS).

Phosphoinositide 3-Kinase (PI 3-Kinase)

An intracellular enzyme recruited and activated by active RTKs that phosphorylates inositol phospholipids in the plasma membrane, generating phosphorylated lipid docking sites that recruit signaling kinases such as Akt.

Akt (Protein Kinase B)

A cytosolic serine/threonine protein kinase recruited to membrane-phosphorylated inositol phospholipids and phosphorylated by protein kinases 1 and 2; active Akt promotes cell survival and growth by phosphorylating downstream targets such as Bad and Tor.

Bad

A cytosolic pro-apoptotic protein that promotes cell death by binding to and inactivating Bcl2; phosphorylation of Bad by active Akt causes Bad to dissociate, freeing active Bcl2 to suppress apoptosis and promote cell survival.

Tor (Target of Rapamycin)

A large serine/threonine protein kinase activated downstream of Akt that enhances cell growth by stimulating protein synthesis and inhibiting protein degradation; it is selectively inactivated by the anticancer drug rapamycin.

Notch Receptor

A transmembrane receptor protein involved in contact-dependent signaling; when bound by the membrane-anchored Delta ligand, a protease cleaves the Notch cytosolic tail, which migrates directly into the nucleus to activate Notch-responsive genes.

Nuclear Receptor Superfamily

A family of intracellular receptor proteins that bind small, hydrophobic hormone molecules (such as cortisol, estradiol, testosterone, and thyroxine) that diffuse across the plasma membrane; hormone binding induces conformational changes, allowing the receptor complex to enter the nucleus and directly regulate target gene transcription.

Plant Ethylene Receptor

An endoplasmic reticulum membrane-bound enzyme-coupled receptor that acts as an off-switch: in the absence of ethylene, the receptor and its associated protein kinase are active, leading to transcription regulator degradation (genes off); binding of ethylene inactivates the receptor and kinase, allowing the transcription regulator to accumulate and activate ethylene-responsive genes.