Finalized Flashcard Set

Chemical messenger

A molecule released by a cell that communicates with target cells.

Ligand

A molecule that binds specifically to a receptor.

Receptor

A protein that recognizes a signaling molecule and initiates a cellular response.

Autocrine signaling

A cell releases a signal that acts on the same cell.

Paracrine signaling

A signal acts on nearby cells.

Endocrine signaling

Hormones travel through the bloodstream to distant target cells.

Synaptic signaling

A neuron releases neurotransmitter across a synapse to a target cell.

First messenger

An extracellular signaling molecule, such as a hormone or growth factor.

Second messenger

An intracellular small molecule or ion that relays and amplifies a signal.

Signal transduction

Conversion of an extracellular signal into intracellular biochemical events.

Amplification

One activated signaling component activates many downstream molecules.

Specificity

A signaling response determined by receptor expression and intracellular pathway components.

GPCR

G-protein-coupled receptor; a membrane receptor that activates heterotrimeric G proteins.

Heterotrimeric G protein

A signaling protein composed of alpha, beta, and gamma subunits.

G alpha subunit

The G-protein subunit that binds GDP/GTP and regulates downstream effectors.

GDP-GTP exchange

Activation step in which GDP on G alpha is replaced by GTP.

GTPase activity

Hydrolysis of GTP to GDP, which helps switch a G protein off.

Adenylyl cyclase

An effector enzyme commonly stimulated by Gαs and inhibited by Gαi. It converts ATP to cAMP, which activates PKA and downstream phosphorylation/transcription responses.

cAMP

A second messenger made from ATP by adenylyl cyclase, commonly activated by Gαs. cAMP activates PKA; phosphodiesterases degrade cAMP and help terminate the signal.

Protein kinase A (PKA)

A cAMP-activated kinase. It phosphorylates target proteins: in liver glycogen metabolism it activates phosphorylase kinase (which activates glycogen phosphorylase) and inhibits glycogen synthase; it can also enter the nucleus and phosphorylate CREB to change transcription.

Phospholipase C (PLC)

An effector enzyme that cleaves membrane PIP2 into IP3 and DAG. IP3 triggers Ca2+ release from the ER, while DAG remains in the membrane and helps activate PKC.

PIP2

Membrane phospholipid cleaved by PLC to generate IP3 and DAG.

IP3

A soluble second messenger produced when PLC cleaves PIP2. IP3 binds IP3 receptors on the ER, opening Ca2+ channels and raising cytosolic Ca2+.

DAG

A membrane-retained second messenger produced by PLC cleavage of PIP2. Together with Ca2+ for conventional PKC isoforms, DAG activates protein kinase C.

Protein kinase C (PKC)

A kinase activated by DAG; conventional PKC isoforms also require Ca2+. PKC phosphorylates downstream proteins to change cellular activity and signaling.

RTK

Receptor tyrosine kinase; a receptor that dimerizes or rearranges and phosphorylates tyrosines after ligand binding.

Autophosphorylation

A receptor or enzyme phosphorylates itself or another subunit of the same complex.

Ras

A membrane-associated small GTPase. Ras-GTP activates Raf, initiating the Raf-MEK-ERK cascade; Ras mutations that impair GTP hydrolysis can keep signaling abnormally active and contribute to cancer.

Raf-MEK-ERK pathway

Ras-GTP activates Raf (MAPKKK), Raf phosphorylates MEK (MAPKK), and MEK activates ERK (MAPK). ERK phosphorylates cytoplasmic targets and can enter the nucleus to alter gene expression.

MAP kinase cascade

Sequential activation of kinases that amplifies and distributes a signal.

JAK-STAT pathway

Cytokine binding brings receptor-associated JAKs into an active arrangement. JAKs phosphorylate receptors and STATs; phosphorylated STATs dimerize, enter the nucleus, and regulate transcription. The slides also note that kinase-associated receptors can activate MAPK signaling.

STAT

Signal transducer and activator of transcription; a protein that can dimerize and enter the nucleus.

Receptor desensitization

Reduced responsiveness after prolonged or repeated stimulation.

Phosphatase

An enzyme that removes phosphate groups from proteins or other molecules.

Mitochondrion

Organelle involved in ATP production, metabolism, and regulation of cell death.

Outer mitochondrial membrane

The relatively permeable outer boundary of mitochondria containing proteins such as VDAC.

Inner mitochondrial membrane

A highly selective membrane containing respiratory-chain complexes and ATP synthase.

Intermembrane space

Compartment between the outer and inner mitochondrial membranes.

Mitochondrial matrix

Innermost compartment containing enzymes, mitochondrial DNA, and ribosomes.

Cristae

Folds of the inner mitochondrial membrane that increase surface area.

Mitochondrial DNA (mtDNA)

Small genome encoding some mitochondrial proteins, rRNAs, and tRNAs.

Mitochondrial targeting sequence

A peptide signal that directs many nuclear-encoded proteins to mitochondria.

TOM complex

Translocase of the outer membrane; helps import proteins into mitochondria.

TIM complex

Translocase of the inner membrane; helps move proteins across or into the inner membrane.

ATP synthase

Enzyme that uses a proton gradient to synthesize ATP.

Chemiosmosis

Use of an electrochemical ion gradient to drive ATP synthesis.

Proton-motive force

Energy stored in the proton electrochemical gradient across the inner mitochondrial membrane.

Mitochondrial fission

Division of one mitochondrion into smaller mitochondria.

Mitochondrial fusion

Joining of mitochondrial membranes to mix contents and maintain mitochondrial function.

Peroxisome

Organelle that carries out oxidative reactions, including very-long-chain fatty-acid breakdown.

Catalase

Peroxisomal enzyme that converts hydrogen peroxide into water and oxygen.

Hydrogen peroxide (H2O2)

Reactive oxygen species produced by several oxidative reactions and detoxified by catalase.

Very-long-chain fatty acids

Fatty acids that are shortened initially in peroxisomes.

Peroxisomal targeting signal

A sequence, often at the protein C-terminus, that directs proteins to peroxisomes.

PEX proteins

Peroxins; proteins required for peroxisome formation and protein import.

Reactive oxygen species (ROS)

Reactive oxygen-containing molecules that can damage cellular components when excessive.

Endoplasmic reticulum (ER)

Membrane network involved in protein synthesis, folding, lipid synthesis, and calcium storage.

Rough ER

ER studded with ribosomes; synthesizes many secreted, membrane, and lysosomal proteins.

Smooth ER

ER region important for lipid synthesis, detoxification, and calcium handling.

Signal recognition particle (SRP)

Recognizes an ER signal sequence and directs the translating ribosome to the ER membrane.

SRP receptor

ER membrane receptor that helps dock the SRP-ribosome complex.

Translocon

Protein-conducting channel that allows a growing polypeptide to enter or insert into the ER membrane.

Co-translational translocation

Movement of a protein into the ER while it is being translated.

BiP

ER-lumen Hsp70 chaperone that assists folding and helps prevent premature or improper interactions.

Protein disulfide isomerase (PDI)

ER enzyme that forms, breaks, and rearranges disulfide bonds.

Disulfide bond

Covalent bond between cysteine side chains that can stabilize protein structure.

ER oxidoreductin-1 (Ero1)

Protein that helps reoxidize PDI so PDI can continue catalyzing disulfide-bond formation.

N-linked glycosylation

Addition of an oligosaccharide to the nitrogen of asparagine, initiated in the ER.

Oligosaccharyltransferase

Enzyme complex that transfers an oligosaccharide to a nascent protein during N-linked glycosylation.

Calnexin

ER membrane lectin chaperone that binds certain glycoproteins during folding.

Calreticulin

Soluble ER lectin chaperone that assists glycoprotein folding.

Unfolded protein response (UPR)

ER stress response that reduces protein-folding load and increases folding capacity.

ER-associated degradation (ERAD)

Quality-control pathway that recognizes misfolded ER proteins and sends them for cytosolic proteasomal degradation.

ER stress

Condition in which misfolded or unfolded proteins accumulate in the ER.

Calcium store

The ER serves as a major intracellular reservoir of Ca2+ in many cells.

Primary structure

The linear amino-acid sequence of a protein.

Secondary structure

Local backbone arrangements such as alpha helices and beta sheets.

Tertiary structure

The overall three-dimensional structure of one polypeptide chain.

Quaternary structure

Arrangement of multiple polypeptide subunits in a functional protein.

Native conformation

The functional, properly folded structure of a protein.

Denaturation

Loss of a protein's higher-order structure without necessarily breaking peptide bonds.

Renaturation

Return of a denatured protein to its native structure under suitable conditions.

Hydrophobic effect

Tendency of nonpolar side chains to be buried away from water during folding.

Molecular chaperone

A protein that assists folding or prevents inappropriate protein interactions without specifying the final structure.

Hsp70

ATP-dependent chaperone family that binds exposed hydrophobic regions of client proteins.

Hsp40

Co-chaperone that helps deliver substrates to Hsp70 and stimulates ATP hydrolysis.

Nucleotide exchange factor (NEF)

Protein that promotes ADP release and ATP binding on Hsp70.

Chaperonin

A protein complex that provides a protected chamber for protein folding.

GroEL

Bacterial chaperonin that encloses a substrate protein in a folding chamber.

GroES

Bacterial co-chaperonin that caps GroEL's folding chamber.

Disulfide isomerization

Rearrangement of disulfide bonds to reach the correct pairing.

Peptidyl-prolyl isomerase

Enzyme that accelerates cis-trans isomerization of peptide bonds involving proline.

Cis-proline

Proline-containing peptide-bond conformation in which adjacent groups are on the same side.

Trans-proline

Proline-containing peptide-bond conformation generally favored in many proteins.

Ubiquitination

Covalent attachment of ubiquitin to a target protein, often marking it for degradation.

Ubiquitin-activating enzyme (E1)

Enzyme that activates ubiquitin using ATP.

Ubiquitin-conjugating enzyme (E2)

Enzyme that carries activated ubiquitin for transfer to a substrate.

Ubiquitin ligase (E3)

Enzyme that recognizes a substrate and helps transfer ubiquitin to it.

Proteasome

Large protease complex that degrades many ubiquitinated proteins.

19S regulatory particle

Proteasome component that recognizes ubiquitin tags, unfolds substrates, and feeds them into the core.