Signaling Transduction

Vocabulary flashcards covering signal transduction pathways, chemical messengers, receptor types, G-protein signaling, secondary messengers, and signal termination.

Cell Signaling

Complex cellular responses triggered by extracellular signals to regulate processes such as differentiation, growth, division, and metabolic regulation.

Primary Signal

An extracellular chemical messenger released to initiate a signal transduction pathway by interacting with specific cell receptors.

Endocrine Signaling

A form of signaling where hormones are secreted into the bloodstream by endocrine glands to act on distant target cells.

Paracrine Signaling

A form of signaling in which a secretory cell releases chemical messengers that diffuse locally to act on adjacent target cells.

Autocrine Signaling

A form of signaling where a cell secretes extracellular signals that bind to receptors located on its own cell membrane.

Signaling by Plasma-Membrane-Attached Proteins

Direct cell-to-cell contact signaling mediated by membrane-attached signal proteins on one cell binding to receptors on an adjacent cell.

Neurotransmitters

Nervous system chemical messengers, such as acetylcholine, epinephrine, and GABA, that transmit signals across synapses.

Polypeptide Hormones

Water-soluble endocrine primary messengers, such as insulin and glucagon, that bind to cell-surface receptors.

Steroid Hormones

Hydrophobic primary messengers, such as cortisol, aldosterone, and sex hormones, that diffuse across membranes to bind intracellular receptors.

Eicosanoids

Lipid-derived primary signaling molecules including prostaglandins, thromboxanes, and leukotrienes.

Cytokines

Immune system primary messengers, such as interleukins, tumor necrosis factors, and interferons, that regulate immune and inflammatory responses.

Growth Factors

Extracellular signaling proteins, such as epidermal growth factor (EGF) and platelet-derived growth factor (PDGF), that stimulate cell proliferation and growth.

Intracellular Receptors

Cytosolic or nuclear receptors that bind hydrophobic signals (e.g., steroid and thyroid hormones) and act directly as transcription factors.

Membrane Receptors

Cell-surface receptors that bind hydrophilic ligands and initiate intracellular signaling cascades via secondary messengers or direct enzymatic activation.

Ion-Channel Receptors

Membrane receptors that undergo conformational changes upon ligand binding to open or close ion channels across the cell membrane.

G-Protein Coupled Receptors

Monomeric heptahelical membrane receptors with seven transmembrane $\alpha$-helical domains that signal through heterotrimeric G-proteins.

Heterotrimeric G-Protein

A membrane-associated signaling complex composed of $\alpha$, $\beta$, and $\gamma$ subunits that acts as a molecular switch downstream of GPCRs.

$G_\alpha$ Subunit

The subunit of a heterotrimeric G-protein that binds GDP in its resting state, exchanges GDP for GTP upon activation, and possesses intrinsic GTPase activity.

$$G_{\alpha s}$$

A class of $G_\alpha$ subunit that activates adenylyl cyclase, leading to increased intracellular levels of cAMP.

$$G_{\alpha i}$$

A class of $G_\alpha$ subunit that inhibits adenylyl cyclase to decrease cAMP levels, and can activate $K^+$ channels via $G_{\beta\gamma}$ subunits.

$$G_{\alpha olf}$$

A class of $G_\alpha$ subunit associated with odorant receptors in the nose that activates adenylyl cyclase to increase cAMP.

$$G_{\alpha q}$$

A class of $G_\alpha$ subunit that activates phospholipase C, leading to increased levels of $IP_3$ and DAG.

$$G_{\alpha o}$$

A class of $G_\alpha$ subunit associated with acetylcholine receptors in endothelial cells that activates phospholipase C to increase $IP_3$ and DAG.

$$G_{\alpha t}$$

A class of $G_\alpha$ subunit (transducin) associated with rhodopsin in rod cells that activates cGMP phosphodiesterase, resulting in decreased cGMP.

Secondary Messengers

Small intracellular molecules or ions, such as cAMP, $IP_3$, DAG, and $Ca^{2+}$, that transduce and amplify signals inside the cell.

Adenylyl Cyclase

A membrane-bound effector enzyme that catalyzes the synthesis of the second messenger cyclic AMP (cAMP) from ATP.

Cyclic AMP

A ubiquitous second messenger generated from ATP by adenylyl cyclase that activates Protein Kinase A (PKA).

cAMP Phosphodiesterase

An enzyme that terminates cAMP signaling by hydrolyzing cAMP into 5'-AMP.

Protein Kinase A

A heterotetrameric enzyme consisting of two regulatory and two catalytic subunits ($R_2C_2$) activated by the binding of cyclic AMP.

Regulatory Subunits of PKA

Subunits of Protein Kinase A that bind four molecules of cAMP, undergoing a conformational change that releases active catalytic subunits.

Phosphoinositide Signaling

A signaling cascade initiated by $G_{\alpha q}$-coupled receptors where phospholipase C cleaves $PIP_2$ into DAG and $IP_3$.

Phospholipase C

An effector enzyme that cleaves membrane phosphatidylinositol 4,5-bisphosphate ($PIP_2$) into diacylglycerol (DAG) and inositol 1,4,5-trisphosphate ($IP_3$).

Phosphatidylinositol 4,5-bisphosphate

A membrane phospholipid ($PIP_2$) cleaved by activated phospholipase C to yield the secondary messengers DAG and $IP_3$.

Diacylglycerol

A hydrophobic secondary messenger (DAG) that remains anchored in the plasma membrane to activate Protein Kinase C (PKC).

Inositol 1,4,5-trisphosphate

A water-soluble secondary messenger ($IP_3$) that diffuses through the cytosol to open ligand-gated $Ca^{2+}$ channels in the endoplasmic reticulum.

Protein Kinase C

A serine/threonine kinase (PKC) activated by DAG and cytosolic $Ca^{2+}$ that phosphorylates downstream protein substrates.

Calmodulin

A ubiquitous intracellular calcium-binding protein that binds four $Ca^{2+}$ ions to change conformation and activate target protein kinases.

Receptor Tyrosine Kinases

Monomeric membrane receptors (RTKs) with a single transmembrane $\alpha$-helix and cytosolic kinase domains that phosphorylate tyrosine residues upon ligand binding.

Autophosphorylation

The cross-phosphorylation of cytosolic kinase domains between dimerized receptor subunits upon extracellular ligand binding.

$SH_2$ Domain

A protein domain that specifically binds to phosphotyrosine residues on activated receptor tyrosine kinases or adaptor proteins.

Grb2

An adaptor protein containing an $SH_2$ domain that binds phosphotyrosine residues on activated RTKs and recruits SOS.

SOS (GEF)

A guanine nucleotide exchange factor recruited by Grb2 to stimulate the exchange of GDP for GTP on Ras.

Ras

A small monomeric G-protein activated by GTP binding downstream of RTKs, which recruits Raf to initiate the MAP kinase pathway.

JAK-STAT Receptors

Cytokine receptors lacking intrinsic enzymatic activity that bind Janus-like kinases (Jak) upon ligand-induced dimerization.

Janus Kinases

Tyrosine kinases (Jak) associated with cytokine receptors that cross-phosphorylate each other, the receptor, and STAT transcription factors.

STAT Proteins

Signal Transducers and Activators of Transcription that are phosphorylated by Jak, form active dimers, and translocate to the nucleus to regulate gene expression.

Serine/Threonine Receptors

Heteromeric cell-surface receptors composed of Type I and Type II subunits that phosphorylate serine residues on target proteins such as Smad.

Smad Proteins

Transcription factor substrates phosphorylated by active Type I serine/threonine receptors that complex with Co-Smad and migrate to the nucleus.

Signal Amplification

The multiplier effect in a transduction cascade where a single primary signal molecule leads to the generation of large numbers of second messengers and activated enzymes.

Protein Phosphatases

Enzymes that terminate signaling by removing phosphate groups from phosphorylated enzymes and transcription factors.