Cell Signaling and Signal Transduction

Vocabulary practice flashcards covering cellular communication, GPCR signaling pathways, second messengers, glycogen metabolism regulation, receptor inactivation, and receptor tyrosine kinase (RTK)-MAPK cascade pathways.

Autocrine signaling

A form of short-range cell signaling in which a cell secretes extracellular chemical signals that bind to receptors on the surface of the same cell.

Paracrine signaling

A form of short-range communication where a cell secretes messenger molecules, such as growth factors or neurotransmitters, that travel through the extracellular space to affect neighboring target cells.

Endocrine signaling

A form of long-range intercellular signaling in which messenger molecules (hormones) are secreted into the bloodstream to reach distant target cells throughout the organism.

Protein kinase

An enzyme that adds a phosphate group to specific target proteins, predominantly at serine, threonine, or tyrosine residues, to alter their activity or interaction properties.

Protein phosphatase

An enzyme that removes phosphate groups from phosphorylated proteins or lipids, typically reversing the action of a kinase and returning targets to an unphosphorylated state.

Phosphatidylinositol (PI)

A membrane lipid substrate that is sequentially phosphorylated on its inositol ring by specific lipid kinases to form $\text{PI(4)P}$ and $\text{PI(4,5)P}_2$.

G protein-coupled receptor (GPCR)

A seven-transmembrane ($\text{7TM}$) receptor with seven $\alpha$-helical transmembrane domains whose extracellular loops bind ligands, driving a conformational change that allows its intracellular domain to activate a heterotrimeric G protein.

Heterotrimeric G protein

A membrane-associated signaling complex consisting of three subunits ($\alpha$, $\beta$, and $\gamma$); inactive when bound to $\text{GDP}$, it releases $\text{GDP}$ and binds $\text{GTP}$ upon activation by a ligand-bound GPCR.

Effector

A downstream enzyme or protein (such as adenylyl cyclase) that binds to an active $\text{G}\\alpha\text{-GTP}$ subunit to propagate signal transduction inside the cell.

Adenylyl cyclase

An effector membrane enzyme activated by $\text{G}\\alpha\text{-GTP}$ that catalyzes the conversion of $\text{ATP}$ into the second messenger cyclic AMP ($\text{cAMP}$).

Cyclic AMP (cAMP)

A small, soluble intracellular second messenger produced from $\text{ATP}$ by adenylyl cyclase that rapidly diffuses away from the plasma membrane to activate downstream enzymes such as protein kinase A.

Protein kinase A (PKA)

A serine/threonine protein kinase activated by binding $\text{cAMP}$ that phosphorylates downstream target enzymes including glycogen synthase, phosphorylase kinase, and the transcription factor CREB.

Glycogen synthase

An enzyme responsible for assembling glycogen that becomes inactivated upon phosphorylation by protein kinase A (PKA) during epinephrine stimulation in the liver.

Phosphorylase kinase

An intermediate enzyme in epinephrine signaling that is phosphorylated and activated by active PKA, subsequently phosphorylating and activating glycogen phosphorylase.

Glycogen phosphorylase

The terminal enzyme in glycogen breakdown that is activated by phosphorylation by phosphorylase kinase to convert glycogen into glucose 1-phosphate.

CREB (cAMP response element-binding protein)

A nuclear transcription factor phosphorylated by active PKA that binds cAMP response elements ($\text{CRE}$) on DNA to regulate gene expression.

Signal amplification

A multi-step cascade mechanism where a single activated receptor stimulates many effector enzymes, producing large amounts of second messengers and yielding a massive cellular output (such as copious glucose from glycogen).

G protein-coupled receptor kinase (GRK)

A specialized kinase mediating fast GPCR inactivation by phosphorylating the cytosolic domain of an activated GPCR to recruit arrestin.

Arrestin

A cytosolic protein that binds specifically to phosphorylated GPCRs to sterically block further G protein activation and facilitate clathrin-mediated endocytosis.

Receptor-mediated endocytosis (of GPCRs)

A slow desensitization pathway in which arrestin recruits a clathrin coat ($\text{AP2}$ and clathrin) to internalize GPCRs into endosomes for continued signaling, lysosomal degradation, or recycling back to the plasma membrane.

Cyclic nucleotide phosphodiesterase

An intracellular enzyme that terminates $\text{cAMP}$ signaling by hydrolyzing $\text{cAMP}$ into $\text{AMP}$.

Retinitis pigmentosa

An inherited retinal disorder characterized by progressive degeneration of the retina and eventual blindness, commonly caused by mutations in the rhodopsin GPCR.

Receptor tyrosine kinase (RTK)

A transmembrane receptor class characterized by an extracellular ligand-binding domain and an intracellular tyrosine kinase domain that dimerizes and undergoes trans-autophosphorylation upon ligand binding.

Trans-autophosphorylation

A process occurring in active RTK dimers where each receptor subunit uses its intracellular kinase domain to phosphorylate specific tyrosine residues on the opposite subunit.

SH2 domain (Src homology 2 domain)

A conserved protein domain that specifically binds to phosphorylated tyrosine residues within defined amino acid sequences on activated receptors or docking proteins.

PTB domain (Phosphotyrosine-binding domain)

A functional protein motif that binds to specific phosphotyrosine-containing sequences on target proteins such as activated RTKs.

Grb2

An adaptor protein containing an SH2 domain and SH3 domains that binds to phosphorylated tyrosines on active RTKs and recruits the exchange factor SOS.

SOS (Son of Sevenless)

A guanine nucleotide exchange factor (GEF) recruited by Grb2 to the plasma membrane, where it catalyzes the exchange of $\text{GDP}$ for $\text{GTP}$ on the small GTPase Ras.

Ras

A membrane-anchored small monomeric GTPase that acts as a binary molecular switch; it is turned on by SOS-mediated exchange of $\text{GDP}$ for $\text{GTP}$ and activates downstream kinase signaling.

Raf

A serine/threonine MAP kinase kinase kinase (MAPKKK) that translocates from the cytoplasm to the membrane upon interacting with $\text{Ras-GTP}$, becoming activated to phosphorylate MEK.

MEK

A dual-specificity MAP kinase kinase (MAPKK) that is phosphorylated and activated by Raf, which then phosphorylates and activates ERK.

ERK

A MAP kinase (MAPK) phosphorylated and activated by MEK that enters the nucleus to phosphorylate transcription factors that regulate cell cycle genes.

MKP-1

A MAP kinase phosphatase whose transcription is activated downstream of ERK signaling to dephosphorylate and inactivate ERK, acting as a negative feedback loop.

Oncogene

A cancer-promoting gene whose mutated or overexpressed protein product (such as constitutively active forms of Ras, Raf, Jun, or Fos) remains persistently turned on.