Signal Transduction Lecture - Molecular and Cellular Mechanisms

Vocabulary flashcards covering key terms and concepts from the lecture notes on signaling pathways, receptors, and related diseases.

Vemurafenib

A targeted inhibitor of the V600E-mutant BRAF kinase used in melanoma; it inhibits the constitutively active BRAF V600E to block the RAF–MAPK signaling cascade.

BRAF V600E mutation

A valine-to-glutamic acid substitution in BRAF that makes BRAF constitutively active, driving MAPK signaling and oncogenesis.

Ras–RAF–MEK–ERK signaling cascade

RTK activation -> Ras -> RAF kinases (ARAF/ BRAF/CRAF) -> MEK -> ERK; ERK moves to the nucleus to regulate transcription factors and promote proliferation/survival.

PI3K–AKT–GSK3 axis

RTK-initiated pathway where PI3K activates AKT, influencing metabolism and survival; AKT modulates downstream targets including GSK3.

RalGDS–Ral–RBP1 axis

Downstream pathway from Ras involving Ral GTPases and RBP1 that affects cytoskeletal dynamics and vesicle trafficking.

RAF kinases (ARAF, BRAF, CRAF)

Kinases that relay RTK signals to the MAPK cascade by phosphorylating MEK.

ERK

Extracellular signal-regulated kinase; activated by MEK; translocates to the nucleus to phosphorylate transcription factors (e.g., Ets, Fos, Elk1, MYC) and regulate gene expression.

Wnt/β-catenin signaling

In the absence of Wnt, β-catenin is degraded; Wnt binding inhibits the destruction complex, stabilizing β-catenin which activates transcription with TCF in the nucleus.

β-catenin/TCF-mediated transcription

β-catenin partners with TCF to drive transcription of Wnt target genes (e.g., Myc), promoting proliferation and survival.

Myc

An oncogenic transcription factor that integrates signals from multiple pathways (Wnt, Ras, Notch, BRCA1, TGF-β, ER-α, EGFR/Her2) to drive proliferation and other cancer hallmarks.

Acromegaly etiology

Growth hormone-secreting pituitary adenoma causing excess GH and elevated IGF-1, leading to acral growth and systemic effects.

GH–IGF-1 axis

GH promotes liver production of IGF-1; IGF-1 mediates growth and metabolic effects in tissues.

Gq/PLCβ/IP3-DAG pathway

GPCR activates Gq; Gq stimulates PLC-β to cleave PIP2 into IP3 and DAG; IP3 releases Ca2+; DAG activates PKC.

IP3

Inositol 1,4,5-trisphosphate; triggers Ca2+ release from the ER via IP3 receptors.

DAG

Diacylglycerol; co-activator with Ca2+ that activates protein kinase C (PKC) in PI signaling.

PKC

Protein kinase C; phosphorylates downstream targets in the DAG/Ca2+ signaling axis.

Gs signaling

GPCR activation of Gs protein stimulates adenylyl cyclase, increasing cAMP and activating PKA.

cAMP

Cyclic adenosine monophosphate; second messenger that activates PKA and other effectors.

Cholera toxin mechanism

ADP-ribosylates Gsα, locking it in GTP-bound form to constitutively activate adenylyl cyclase, raising cAMP and activating CFTR via PKA.

Gq vs Gs signaling difference

Gq activates PLC to generate IP3/DAG (Ca2+ release and PKC); Gs activates adenylyl cyclase to raise cAMP.

β-adrenergic signaling

Catecholamines bind β-adrenergic receptors (Gs-coupled) to raise cAMP and activate PKA, influencing CREB/AP-1 and gene expression.

Propranolol

Non-selective β-adrenergic receptor antagonist that blocks β signaling, reducing cAMP/PKA activity.

NF-κB canonical pathway

TNF-α/TNFR or IL-1R activation → IKK complex phosphorylates IκB → IκB degradation → NF-κB (p65/p50) enters nucleus to promote inflammatory gene transcription.

NF-κB non-canonical pathway

BAFFR/CD40/RANK activate NIK → IKKα → processing of p100 to p52; p52/RELB enters nucleus to regulate gene expression.

RhoA/ROCK pathway

RhoA-GTP activates ROCK; ROCK inhibits MLCP by MLCP regulation and phosphorylates MLC, increasing actomyosin contraction; LIMK phosphorylates cofilin to stabilize F-actin.

RhoA/ROCK in vascular disease

Increased ROCK activity promotes vascular smooth muscle contraction and endothelial dysfunction in atherosclerosis.

NO–cGMP–PKG pathway

NO produced by eNOS diffuses to smooth muscle, activates soluble guanylyl cyclase, increasing cGMP; cGMP activates PKG leading to vasodilation and antithrombotic effects; NO bioavailability is reduced in atherosclerosis.