Signal Transduction Lecture: Molecular and Cellular Mechanisms

Vocabulary flashcards covering key signaling pathways, receptors, and disease mechanisms from the lecture notes.

Vemurafenib

A selective inhibitor of the BRAF V600E mutant kinase that blocks aberrant MAPK/ERK signaling in melanoma.

BRAF V600E

BRAF mutation (valine to glutamic acid) that yields a constitutively active kinase driving MAPK pathway signaling.

RAS

Small GTPase activated by RTKs via Grb2/SOS; toggles between inactive GDP-bound and active GTP-bound forms.

Grb2

Adaptor protein linking activated RTKs to SOS, initiating RAS activation.

SOS

Guanine nucleotide exchange factor that promotes GDP→GTP exchange on RAS, activating it.

RAF kinases (ARAF, BRAF, CRAF)

Kinases that relay signals from RAS to MEK in the MAPK cascade.

MEK

Dual-specificity kinase that phosphorylates and activates ERK in the MAPK pathway.

ERK

MAP kinase that phosphorylates transcription factors and regulates gene expression for proliferation and survival.

MAPK cascade

Signaling module: RAF → MEK → ERK, transmitting mitogenic signals to the nucleus.

ERK targets (Ets, Fos, Elk1, MYC, Cyclin D, GLUT1, ER/EP-1)

Transcription factors and genes activated by ERK to drive proliferation, metabolism, and hormone response.

PI3K–AKT–GSK3

Pathway downstream of RTKs promoting cell survival and metabolism via AKT and GSK3 regulation.

RalGDS–Ral–RBP1

MAPK‑alternative branch influencing cytoskeletal dynamics and vesicle trafficking.

NO (nitric oxide)

Gaseous signaling molecule produced by NOS that promotes vasodilation.

eNOS

Endothelial nitric oxide synthase; generates NO in blood vessels from L-arginine.

Guanylyl cyclase

Enzyme activated by NO to convert GTP to the second messenger cGMP.

cGMP

Second messenger that activates PKG, promoting smooth muscle relaxation and anti-platelet effects.

PKG

Protein kinase G; phosphorylates targets (e.g., VASP) to reduce Ca^{2+} and induce relaxation.

NO bioavailability

Amount of NO available to stimulate guanylyl cyclase; reduced in endothelial dysfunction and atherosclerosis.

Wnt canonical pathway

Wnt signaling that stabilizes β-catenin by inhibiting the destruction complex, enabling β-catenin–TCF–LEF transcription.

β-catenin–TCF/LEF

Stabilized β-catenin enters the nucleus to partner with TCF/LEF and drive target gene transcription.

Destruction complex (Axin, APC, CKI, GSK3)

Complex that phosphorylates β-catenin, marking it for ubiquitination and degradation in the absence of Wnt.

β-TrCP

E3 ubiquitin ligase that targets phosphorylated β-catenin for proteasomal degradation.

Myc hub

Myc integrates signals from Wnt, Ras, Notch, BRCA1, TGF-β, ER-α, EGFR/Her2 to drive proliferation and cancer hallmarks.

APC (destruction complex component)

Tumor suppressor protein in the β-catenin destruction complex; its mutation contributes to colorectal cancer.

β-catenin activation in colon cancer

Constitutively active β-catenin binds DNA with TCF/LEF to drive oncogenic transcription.

GH/IGF-1 axis in acromegaly

Pituitary GH excess stimulates hepatic IGF-1 production; IGF-1 mediates somatic overgrowth symptoms.

IGF-1

Insulin-like growth factor 1; mediator of growth effects, elevated in acromegaly.

α1-adrenergic receptor signaling

Gq‑coupled receptor; activates PLCβ → IP_3 and DAG; Ca^{2+} release and PKC activation.

Gq/PLCβ/IP3-DAG pathway

GPCR pathway where Gq activates PLCβ to produce IP_3 and DAG, elevating Ca^{2+} and activating PKC.

Cholera toxin mechanism

A1 subunit ADP-ribosylates Gsα, locking it in the GTP-bound state and constitutively activating adenylyl cyclase to raise cAMP.

Gq vs Gs differences

Gq activates PLCβ to raise IP_3/DAG and Ca^{2+}; Gs activates adenylyl cyclase to raise cAMP.

β-adrenergic signaling (cAMP/PKA/MAPK)

Catecholamines bind β receptors (Gs) → ↑cAMP → PKA and MAPK activation; influences CREB, AP-1 transcription factors.

Propranolol

Non-selective β-adrenergic receptor antagonist; reduces cAMP/PKA signaling to blunt sympathetic effects.

NF-κB canonical pathway

TNF-α/TNFR or IL-1R activation → IKK-mediated IκB phosphorylation/degradation → NF-κB (p65/p50) nuclear transcription of inflammatory genes.

NF-κB non-canonical pathway

BAFFR/CD40/RANK activate NIK → IKKα → processing of p100 to p52; p52/RELB nuclear transcription.

RhoA/ROCK pathway

RhoA-GTP activates ROCK; ROCK inhibits MLCP and phosphorylates MLC, increasing contraction and stabilizing actin via LIMK.

RhoA/ROCK in atherosclerosis

Elevated ROCK activity contributes to vascular smooth muscle contraction and endothelial dysfunction.

PTSD and β-adrenergic signaling

Chronic norepinephrine → β‑receptor/cAMP/PKA affects memory consolidation and relearning; propranolol can blunt reconsolidation.

Fight-or-Flight to PTSD summary

Acute β-adrenergic signaling drives arousal; chronic activation can reinforce fear memories and anxiety; β-blockers may mitigate symptoms.