Signal 2

From CellBiology

Cell Signaling 2

This lecture is the second in a series of lectures on cell signaling. The first lecture was a general introduction to the different signaling mechanisms and steroid pathways. The following lecture looks in detail at two specific examples of signaling pathways: G Protein-Coupled Signal and Receptor Tyrosine Kinases. Note that you have already been introduced to signaling in many of your other lecture topics and the lectures on stem cells and development will further discuss cell signaling events.

Archive: 2016 | 2015 | 2013

Signal transduction pathways.png


Table 20-1. Characteristic Properties of Principal Types of Mammalian Hormones

Classes of Surface receptor

G Protein-Coupled Signal Pathways

Begin by looking at Figure 20-6. Schematic overview of common signaling pathways downstream from G protein–coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs)

Activation of adenylyl cyclase following binding to a Gs protein – coupled receptor

G-protein-coupled receptor structure G-protein coupled receptors
G-protein-coupled receptor structure G-protein coupled receptors
  • Transmembrane proteins transduce extracellular signals
  • common structural motif of 7 membrane spanning regions
  • Receptor binding promotes interaction
    • between receptor
    • G protein on interior surface of membrane
  • induces an exchange of GDP for GTP on G protein α subunit and dissociation of the α subunit from the βγ heterodimer

GTP-α subunit complex mediates intracellular signaling, depending on isoform either

  • indirectly - by acting on effector molecules adenylyl cyclase (AC), phospholipase C(PLC)
  • directly - by regulating ion channel or kinase function

Receptor associated with Kinase

Receptor and non-receptor tyrosine kinases
Endothelial cell signaling cartoon

Many growth factors use this pathway

  • Vascular Endothelial Growth Factor (VEGF)
  • Epidermal Growth Factor (EGF)
  • Nerve Growth Factor (NGF)
  • Bone Morphogenic Protein (BMP)
  • Transforming Growth Factor-beta (TGF-beta)


  1. Ligand binding
  2. Receptor association
  3. Phosphorylation
  4. Kinase cascade

VEGF Receptor and Ligands (example) EGF Receptor Transduction Pathway Signaling Pathway of TGF-β

  • TGF-β receptor
  • include Type I and II subunits
  • are serine-threonine kinases
  • signal through SMAD family of proteins
  • binding of TGF-β to cell surface receptor Type II leads to phosphorylation of Type I receptor by Type II

TrkA Receptor

TrkA receptor.jpg The PI 3-kinase pathway and cell survival

  • trk (often pronounced 'track') stands for tropomyosin-receptor-kinase (not tyrosine kinase or tropomyosin-related kinase)
  • proteins with a single transmembrane helix
  • Trk proto-oncogenes – TrkA, TrkB, TrkC, TrkE
    • variably expressed in CNS and PNS

TrkA Pathway

  1. following neurotrophin binding
  2. dimeric Trk receptors
  3. phosphorylate one another at tyrosine residues (Y490 and Y785 for TrkA)
  4. phosphotyrosines bind adaptor molecules such as Shc and PLC-γ.
  5. these signaling intermediaries activate three major signaling pathways
    1. Ras/MAPK cascade
    2. PI3K/AKT
    3. IP3-dependent Ca2+ release (?)
  6. pathway activation results in transcriptional changes of different target genes


Links: Neurotrophin–receptor interactions | Neurotrophin signalling


  • Normal cell proteins that have potential to cause uncontrolled growth when mutated
    • loss of receptor regulation
    • cells grow out of control
    • mutation in TK Receptor – receptor always activated
    • mutation of activating protein – always active
    • Oncogenes – Ras
  • mutants detected in 30% cervical cancers

Movie: Methods Receptor/Ligand MCB

Movie: Receptor Internalization


The mechanism for dephosphorylation is through phosphatases.

Three main families of phosphatases

  1. phospho-Tyr phosphatases (PTP)
  2. phospho-Ser/Thr phosphatases
  3. those that cleave both

Phosphatase specificity by binding protein cofactors

  • facilitate translocation and binding to specific phosphoproteins
  • active phosphatase consists of a complex
    • phosphatase catalytic subunit
    • regulatory subunit
  • Regulatory subunits for Tyr phosphatases may contain a SH2 domain allowing binding of the binary complex to autophosphorylated membrane receptor Tyr kinases.

Protein Tyr phosphatases (PTPs)

  • consist of receptor-like (transmembrane) and intracellular Tyr phosphatases (about 100 PTPs)

PTP1B - dephosphorylates many cell surface receptors (insulin, EGF, PDGF) that have been phosphorylated on Tyr residues



Essential Cell Biology

  • Essential Cell Biology Chapter 15

Molecular Biology of the Cell

Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter New York and London: Garland Science; c2002

Molecular Cell Biology

Lodish, Harvey; Berk, Arnold; Zipursky, S. Lawrence; Matsudaira, Paul; Baltimore, David; Darnell, James E. New York: W. H. Freeman & Co.; c1999

The Cell- A Molecular Approach

Cooper, Geoffrey M. Sunderland (MA): Sinauer Associates, Inc.; c2000

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2017 Course Content


Lectures: Cell Biology Introduction | Cells Eukaryotes and Prokaryotes | Cell Membranes and Compartments | Cell Nucleus | Cell Export - Exocytosis | Cell Import - Endocytosis | Cytoskeleton Introduction | Cytoskeleton - Microfilaments | Cytoskeleton - Microtubules | Cytoskeleton - Intermediate Filaments | Cell Mitochondria | Cell Junctions | Extracellular Matrix 1 | Extracellular Matrix 2 | Cell Cycle | Cell Division | Cell Death 1 | Cell Death 2 | Signal 1 | Signal 2 | Stem Cells 1 | Stem Cells 2 | Development | 2017 Revision

2017 Laboratories: Introduction to Lab | Fixation and Staining |

2017 Projects: Group 1 - Delta | Group 2 - Duct | Group 3 - Beta | Group 4 - Alpha

Dr Mark Hill 2015, UNSW Cell Biology - UNSW CRICOS Provider Code No. 00098G