GPCRs, RTKs, second messengers, MAPK, PI3K-AKT, Wnt/Hh/Notch, TGF-β, mTOR, ubiquitin-proteasome.
Cell Signaling
Signal transduction
Cascade of molecular events converting extracellular signal (ligand) into intracellular response. Receptor → effectors → second messengers…
G-protein coupled receptor (GPCR)
Largest receptor family (~800 in humans): 7-transmembrane-helix receptors coupling ligand binding to heterotrimeric Gα/β/γ activation.…
Second messenger
Small diffusible intracellular molecule amplifying receptor signal: cAMP, cGMP, Ca²+, IP3, DAG, PIP3, NO. Concept introduced by Sutherland…
Receptor tyrosine kinase (RTK)
Single-TM receptors that dimerise on ligand binding, trans-autophosphorylate cytoplasmic Tyr residues recruiting SH2-domain effectors.…
MAPK cascade
Three-tier kinase cascade: MAPKKK → MAPKK → MAPK (e.g. Raf → MEK → ERK). Downstream of RTKs via Ras; drives proliferation, differentiation.…
PI3K-AKT pathway
PI3K phosphorylates PIP2→PIP3; AKT/PKB bound via PH domain, phosphorylated by PDK1 + mTORC2. Drives survival, growth, metabolism. PTEN…
Wnt pathway (canonical)
Wnt ligand binds Frizzled + LRP5/6, inhibits GSK3β-mediated β-catenin degradation. β-catenin accumulates, enters nucleus, partners with…
Notch pathway
Juxtacrine signalling: Delta/Jagged ligand on neighbour cell activates Notch receptor by triggering S2 (ADAM) + S3 (γ-secretase) cleavages.…
TGF-β pathway
TGF-β superfamily (TGF-β, BMP, activin) binds type-II/I Ser/Thr-kinase receptors; phosphorylates R-SMADs which partner with Co-SMAD4 →…
mTOR pathway
mTOR kinase forms mTORC1 (rapamycin-sensitive, growth/metabolism via S6K + 4E-BP1) + mTORC2 (rapamycin-resistant, cytoskeleton + AKT).…
Ubiquitin-proteasome system
E1 → E2 → E3 cascade appends ubiquitin to substrate (K48-polyUb) for 26S proteasomal degradation. Regulates cell cycle, signalling, MHC-I…
GPCR / second-messenger cascade framework
G-protein-coupled receptor activation triggers GDP→GTP exchange on Gα subunit, Gα-GTP dissociates from Gβγ, modulates downstream effectors…
GPCR signaling (Lefkowitz-Kobilka)
Lefkowitz-Kobilka Nobel 2012: GPCRs 7TM heterotrimeric Galphabetagamma activation -> beta-arrestin desensitization; ~30% of FDA drugs…
Ras-MAPK signaling cascade
Sturgill-Cobb 1988 + Marshall 1995 ERK1/2: RTK -> Ras-GTP -> Raf -> MEK -> ERK -> nuclear-targets; dual-phosphorylation amplification;…
PI3K-Akt-mTOR (survival pathway)
Cantley 1988 PI3K + mTOR (Schreiber 1991 / Sabatini 2002): phosphatidyl-inositol 3-kinase generates PIP3; Akt activation; mTORC1/2 control…
Wnt/beta-catenin (developmental)
Nusse-Varmus 1982 Int-1/Wnt + McMahon 1990s canonical pathway: Wnt-Frizzled -> Disheveled -> beta-catenin stabilization -> LEF/TCF…
Notch signaling (juxtacrine)
Wharton-Artavanis-Tsakonas 1985 Notch + 1990s Greenwald-Rubin: ligand-induced gamma-secretase NICD cleavage -> nuclear-CSL transcription;…
NF-kB inflammation signaling
Sen-Baltimore 1986 NF-kB: TNFalpha/IL1/LPS -> IKK -> IkappaBalpha phosphorylation/degradation -> p50-p65 nuclear translocation; canonical +…
PI3K-Akt-mTOR pathway
Cantley 1988 PI3K + mTOR Schreiber 1991 / Sabatini 2002; modern rapamycin + everolimus + AZD8055 clinical-trials.
Ras-MAPK signaling
Sturgill-Cobb 1988 + Marshall 1995; modern KRAS-G12C sotorasib + adagrasib FDA 2021-2022 first-in-class.
JNK stress (Davis 1993)
R Davis 1993 JNK; modern stress-activated-MAPK + apoptosis decision; cancer + neurodegeneration.
NF-κB canonical/non-canonical
Sen-Baltimore 1986 + Bonizzi-Karin 2004 non-canonical; modern IKK + ubiquitin-proteasome targets.
PKA / cAMP (Sutherland 1971)
E Sutherland 1971 (Nobel 1971) cAMP second-messenger; modern PKA-AKAP + EPAC; broad signaling network.
Hedgehog (Nüsslein-Volhard 1980)
Nüsslein-Volhard-Wieschaus 1980 (Nobel 1995) hedgehog-segment-polarity; modern smoothened-inhibitor vismodegib 2012.