Cell Signaling and Cytoskeleton Practice Flashcards

Vocabulary flashcards covering cell signaling pathways (GPCR, RTK, JAK-STAT, PI3K-AKT, TGF-beta, canonical developmental pathways) and actin cytoskeletal dynamics from Lectures 17-20.

Ligand

A particular type of organic molecule synthesized within the cell (such as a hormone or small protein) that functions as an allosteric regulator by binding to a receptor, triggering a cascade effect that activates or deactivates biological processes.

Hydrophobic Ligands

Molecules such as steroids and retinoids that diffuse directly through the plasma membrane to bind intracellular receptors, which often function directly as transcription factors.

Hydrophilic Ligands

Polar proteins or peptides that cannot diffuse across the plasma membrane and require integral transmembrane receptors to transduce their extracellular signal into the cell.

Effector

A specific enzyme or ion channel in a G-protein coupled receptor pathway that is activated by G proteins and is directly responsible for producing or releasing secondary messengers.

Endocrine Signaling

A form of long-distance signaling in which signaling molecules are synthesized and secreted by signaling cells to act on distant target cells.

Paracrine Signaling

Localized signaling where a cell releases signaling molecules to affect neighboring cells in the immediate environment.

Autocrine Signaling

Self-signaling in which a cell synthesizes and secretes a ligand that binds to and activates receptors on the exact same cell that produced it.

Juxtacrine Signaling

A form of signaling requiring direct physical cell-to-cell contact, occurring when a membrane-bound protein on one cell binds noncovalently to a receptor on an adjacent cell.

Guanine Nucleotide Exchange Factors (GEFs)

Allosteric regulators that promote the activation of G proteins by stimulating the release of bound GDP to allow GTP to bind.

GTPase Activating Proteins (GAPs)

Proteins that stimulate the intrinsic GTPase activity of G proteins, accelerating the hydrolysis of GTP to GDP to turn the G protein off.

Guanine Nucleotide-Dissociation Inhibitors (GDIs)

Allosteric inhibitors that bind to inactive G proteins and prevent the release of GDP, maintaining the G protein in an inactive state.

Heterotrimeric G Protein

A complex composed of alpha, beta, and gamma subunits that functions with GPCRs; the alpha and gamma subunits are lipid-anchored, and upon GTP binding, the alpha subunit separates from the beta-gamma dimer.

Secondary Messengers

Small intracellular molecules synthesized by enzymes or ions released by ion channels (such as cAMP, cGMP, IP3, DAG, and $Ca^{2+}$) that rapidly diffuse through the cytoplasm to allosterically regulate target proteins.

Dissociation Constant ($K_d$)

A quantitative measure of the affinity between a receptor and its ligand; a lower $K_d$ indicates higher receptor affinity, whereas a higher $K_d$ reflects lower affinity.

Agonist

A synthetic ligand structurally similar to a natural endogenous ligand that binds to and activates a receptor.

Antagonist

A synthetic ligand that mimics the structure of an endogenous ligand and binds to the receptor without activating it, acting as an allosteric inhibitor or blocker.

Phosphatidylinositol (PI)

A standard membrane phospholipid characterized by an inositol sugar polar head group that functions as a structural component and can be phosphorylated into signaling phosphoinositides.

Phospholipase C (PLC)

An effector enzyme activated by G proteins that cleaves the phosphorylated inositol residue from the diacylglycerol backbone of membrane phosphoinositides, yielding DAG and IP3.

Diacylglycerol (DAG)

A membrane-bound secondary messenger containing two fatty acid tails that, in cooperation with $Ca^{2+}$, recruits and activates Protein Kinase C (PKC) at the cytoplasmic face of the membrane.

Inositol 1,4,5-trisphosphate (IP3)

A soluble secondary messenger generated by PLC cleavage that diffuses through the cytoplasm to bind and open ligand-gated calcium channels in the endoplasmic reticulum membrane.

Calmodulin

A calcium-binding accessory and scaffolding protein that changes conformation upon binding $Ca^{2+}$ to become an allosteric regulator of downstream proteins such as calmodulin-dependent protein kinases.

Receptor Tyrosine Kinases (RTKs)

Single-pass cell-surface receptors containing an extracellular ligand-binding domain and an intrinsic cytoplasmic tyrosine kinase domain that phosphorylates tyrosine residues following ligand-induced dimerization.

Cytokine Receptors

Cell-surface receptors lacking intrinsic kinase activity that function in complex with a tightly bound, separate cytoplasmic tyrosine kinase (such as JAK).

Trans-Autophosphorylation

A process in which dimerized kinase receptors reciprocally phosphorylate the kinase domains and cytoplasmic tails of their binding partners rather than phosphorylating themselves.

SH2 (Src Homology 2) Domain

A protein interaction domain that recognizes and binds a four-amino-acid motif wherein the phosphorylated tyrosine residue is the first amino acid in the sequence.

PTB (Phosphotyrosine-Binding) Domain

A protein interaction domain that recognizes and binds a four-amino-acid motif wherein the phosphorylated tyrosine residue is the last amino acid in the sequence.

Adapter Proteins

Linker proteins, such as Grb2, that bind to phosphorylated tyrosines on activated receptors via SH2 or PTB domains to recruit exactly one additional signaling protein to the membrane.

Docking Proteins

Proteins that bind to activated receptors and possess multiple tyrosine residues that get phosphorylated, functioning like a power strip to recruit multiple signaling proteins simultaneously.

Ras

A lipid-anchored monomeric G protein in RTK signaling pathways that is activated by GEFs like SOS to allosterically activate the MAP kinase cascade.

MAP Kinase Cascade

A three-tier phosphorylation cascade comprising MAP3K (Raf), MAP2K (MEK), and MAP1K (ERK) that transmits and amplifies upstream signals to regulate transcription factors and cellular responses.

Scaffolding Proteins

Proteins that physically tether and orient specific signaling cascade components (such as MAP kinases) to ensure proper pathway assembly and prevent improper crosstalk.

Phosphoinositide 3-Kinase (PI3K)

An enzyme recruited downstream of RTKs or GPCRs that phosphorylates the third carbon of the inositol ring of membrane phosphoinositides to generate recruitment sites for Protein Kinase B.

Protein Kinase B (PKB / AKT)

A cytosolic kinase recruited to the plasma membrane by PI3K-phosphorylated phosphoinositides, where it is activated by PDK1 and PDK2 to regulate cell survival, growth, and division.

PTEN

The reciprocal phosphatase for PI3K that dephosphorylates the third carbon of the inositol ring, downregulating the PI3K-AKT pathway.

TGF-$\beta$ Receptors

Serine/threonine kinase cell-surface receptors (R1, R2, R3) that bind dimeric TGF-$\beta$ ligands and trans-phosphorylate to activate downstream SMAD transcription factors.

SMAD

A transcription factor that is phosphorylated by the activated R1 subunit of the TGF-$\beta$ receptor, exposing a nuclear localization signal to enter the nucleus and regulate extracellular matrix genes.

Frizzled

The cell-surface receptor for Wnt ligands that recruits the $\beta$-catenin destruction complex to the membrane upon activation.

$\beta$-Catenin

A key regulatory protein in Wnt signaling that is constitutively targeted for proteasomal degradation when the pathway is off, but accumulates and enters the nucleus to coactivate TCF when Wnt is bound.

Groucho

A transcriptional repressor that binds to the transcription factor TCF in the nucleus when Wnt signaling is inactive, blocking target gene transcription.

Morphogen

A signaling molecule, such as Hedgehog, produced in a localized source that diffuses across a tissue to establish a concentration gradient directing distinct developmental outcomes at different thresholds.

Autoproteolysis

A post-translational self-cleavage reaction in which a protein precursor cleaves its own peptide backbone, as occurs during the maturation of the Hedgehog ligand.

Patched (PTCH)

The transmembrane receptor for Hedgehog that prevents vesicles containing Smoothened from fusing with the plasma membrane in the absence of ligand.

Smoothened (SMO)

A transmembrane protein in the Hedgehog pathway that translocates to the cell membrane upon Patched internalization to disrupt the complex responsible for cleaving Ci/Gli.

Ci / Gli

A transcription factor in Hedgehog signaling that is proteolytically cleaved into a repressor when the pathway is off, but enters the nucleus full-length as an activator when Hedgehog is present.

$$NF\text{-}\kappa B$$

A master transcription factor composed of p50 and p65 subunits that remains sequestered in the cytoplasm until its bound inhibitor is polyubiquitinated and degraded.

$$I\kappa B\alpha$$

An inhibitory protein that binds to $NF\text{-}\kappa B$ in the cytoplasm; its targeted degradation by the proteasome frees $NF\text{-}\kappa B$ to translocate to the nucleus.

Regulated Intramembrane Proteolysis

A signaling mechanism involving the sequential controlled cleavage of an integral membrane receptor (such as Notch by ADAM) to release an active soluble domain into the cytoplasm and nucleus.

Signal Divergence

A signaling phenomenon where the activation of a single ligand-receptor interaction leads to multiple distinct biological responses within a cell or across different cell types.

Signal Convergence

A signaling phenomenon in which multiple different cell-surface receptors and pathways activate the same downstream signaling intermediate to produce the same biological outcome.

G-Actin

Globular, monomeric actin that binds ATP and serves as the fundamental building block that polymerizes into microfilaments.

F-Actin

Filamentous actin consisting of two protofilaments twisted into a double-stranded helical microfilament with structural polarity.

Critical Concentration ($C_c$)

The threshold concentration of free, ATP-bound G-actin monomers required for microfilament assembly to occur ($0.12\,\mu M$ at the plus end and $0.60\,\mu M$ at the minus end).

Actin Treadmilling

A steady-state force-generating process in which actin monomers are continuously added to the plus end and lost from the minus end, maintaining constant overall filament length.

Profilin

An actin-regulatory protein that acts like a nucleotide exchange factor by promoting the exchange of ADP for ATP on G-actin, accelerating microfilament polymerization.

Cofilin

An actin-binding protein that binds ADP-actin subunits near the minus end of microfilaments to promote subunit dissociation and filament breakdown.

Thymosin $\beta\text{-}4$

An actin-buffering protein that binds to ATP-bound G-actin to sequester it, preventing polymerization until the free monomer pool needs replenishment.

CapZ

A capping protein that binds specifically to the plus end of an actin microfilament, preventing the addition or removal of actin monomers at that end.

Gelsolin

An actin-regulatory protein that severs actin microfilaments and remains bound to cap the newly exposed plus end, effectively shortening the filament.

Tropomyosin

A regulatory protein that caps the minus end of actin filaments to stabilize them and, in relaxed muscle, lies along actin filaments to block myosin-binding sites.

Formins

Actin nucleation proteins activated by Rho-family G proteins that initiate the de novo assembly of brand-new, unbranched actin filaments.

ARP2/3 Complex

An actin nucleation complex that binds to existing actin microfilaments to initiate new branching filament networks.

Sarcomere

The repeating contractile unit of a muscle myofibril, bounded at both ends by Z discs and composed of interdigitating actin thin filaments and myosin II thick filaments.

Nebulin

A protein in the sarcomere that wraps around thin actin filaments, functioning as a molecular ruler to determine and maintain their precise length.

Titin

A giant, highly elastic protein in the sarcomere that connects thick filaments to the Z disc, acting like a spring to prevent muscle overstretching.

Troponin

A calcium-binding complex in muscle that undergoes a conformational change upon binding $Ca^{2+}$, displacing tropomyosin to expose myosin-binding sites on actin.

Chemotaxis

The directional migration of a cell along or against an extracellular chemical gradient detected by specialized cell-surface receptors.