Receptors and Signal transduction

Min‐Chuan Huang

mchuang@ntu edu twmchuang@ntu.edu.tw

1Molecular Cell Biology 6th ed. Lodish et al.

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I ll l i li hIntracellular signaling pathways

• Kinases and phsphatases

GTP f il• GTPase superfamily

• Second messengers• Second messengers

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Kinases vs. phosphatases

Journal of Cell Science 121, 551-559 (2008)

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GTPase superfamilyp y

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Second messengers

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cAMPPKA‐AKAP‐Effector

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Eight major classes of cell surface receptors

TNFαTNFαreceptors

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G-protein-coupled receptor (GPCR) signaling

Internalization

Scaffold proteins signaling

RGS

GRKPKAPKC

RGS

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Modified from TRENDS in Pharmacological Sciences Vol.22 No.7 July 2001, 368-376

TGFβ and TGFβ receptors

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Activated TGFβ receptors phosphorylate Smadtranscription factorstranscription factors

R‐Smads: receptor‐regulated Smads(Smad2, Smad3, Smad1, Smad5, Smad8/9)( , , , , / )

Co‐Smads: common‐mediated Smads(Smad4)

I Smads: inhibitory SmadsI‐Smads: inhibitory Smads(Smad6, Smad7)

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Downregulation of Smad transcription activationfunction(Ski d S )(Ski and Sno)

19Ski, Sno, and I‐Smads are negative regulators in TGFβ signaling

Cytokine Receptors and the JAK/STAT Pathway

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Activation of Cytokine Receptors

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Activation of STAT proteins

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Termination of EpoR signaling

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Receptor Tyrosine Kinases

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Ligand‐induced dimerization of HER1

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The HER family of receptors and their ligands

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Activation of Ras

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Ras/MAP kinase pathway

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MAP kinase regulates the activity of transcription factors controlling early‐response genesfactors controlling early response genes

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The canonical Wnt signalling pathwayThe canonical Wnt signalling pathway

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Nat Rev Mol Cell Biol. 2010 Jun;11(6):404-13.

Hedgehog (Hh) signalling pathwayHedgehog (Hh) signalling pathway

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TNF‐α/NF‐κB signalling pathway

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Notch signalling pathway

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