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BCHOBI 812

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Rhodopsin: A specialized 7TM receptor mediating the visual cycle: ... Lysine-296 of rhodopsin forms a protonated Schiff base with 11-cis-retinal in the dark: ... – PowerPoint PPT presentation

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Title: BCHOBI 812


1
BCH/OBI 812 September 23/24, 2002 C. Waechter
SIGNAL TRANSDUCTION PATHWAYS (Stryer-Chapter
15) General principles of signal transduction
Biochemical communication between the outside and
inside of animal cells
Hormones Neurotransmitters Growth
factors Differentiation factors
7TMs Tyrosine kinase receptors
Heterotrimeric/ monomeric G Proteins Protein
kinases PKC PKA
2
Common second messengers mediating
intracellular communication
3
Protein phosphorylation Mechanism for
information transfer
3. Protein phosphorylation is a common means of
information transfer. Many second messengers
elicit responses by activation protein kinases.
These enzymes transfer phosphoryl groups from ATP
to specific serine, threonine, and tyrosine
residues in proteins.
4
  • Seven-transmembrane (7TM) -helix
    receptors change conformation in response to
    binding external ligands and activate G-proteins
  • Some hormones using cAMP as a second messenger
  • 1. Epinephrine
  • 2. Glucagon
  • 3. Follicle-stimulating hormone
  • 4. Calcitonin
  • 5. Parathyroid hormone
  • General structure of 7TM receptors

5
Role of heterotrimeric G-protein in the
activation of adenyl cyclase Stimulation of
glycogen breakdown by epinephrine (Stryer-p. 587)
(64 kDa)
Hydrolysis by GTPase acctivity
Phosphorylates Ser/Thr residues in Target
proteins
6
ACTIVATION OF PKA BY cAMP
7
Signal termination by phosphorylation and
arrestin-binding
8
Cleavage of phosphatidylinositol bisphosphate
(PIP2) by phospholipase Cb produces two second
messengers, IP3 and diacylglycerol (DAG)
(ER)
Activated by C Ca DAG PS
9
Modular structures of phospholipase Cs
10
Modular structures of protein kinase Cs (PKC)
Activation by DAG/PS/Ca
DAG
PS/Ca
Ala replaces Ser/Thr
Phosphorylates Ser/Thr residues in Target proteins
PS
11
Binding of EGF to its receptor leads to
activation of Ras, a monomeric G-protein, via
interactions with SH2 domains.
Ras 20-25 kDa small monomeric G protein
Grb-2
12
Rhodopsin A specialized 7TM receptor mediating
the visual cycle Anatomy of a rod cell
(Stryer-p. 908)
13
Lysine-296 of rhodopsin forms a protonated Schiff
base with 11-cis-retinal in the dark
Isomerization of 11-cis-retinal to
11-trans-retinal is triggered by photons
14
Conversion of rhodopsin to metarhodopsin II (R)
activates heterotrimeric G-protein called
transducin which stimulates phosphodiesterase
Plasma membrane Of outer segment
Disc membrane
15
Hydrolysis of cGMP closes cGMP-gated channel,
resulting in lower cytosolic Ca levels
hyperpolarization of retinal rod cell membrane
triggers neuronal signalling
16
Mechanism for re-setting visual cycle
  • Hydrolysis of GTP on a-subunit.
  • Phosphorylation of cytoplasmic loop
  • of rhodopsin (opsin) allowing b-arrestin
  • to bind.
  • Re-synthesis of cGMP by guanyl cyclase
  • is stimulated by lower Ca levels.

17
Recovery mechanism Lower Ca increases guanyl
cyclase activity restoring cGMP levels and
re-opening of cGMP-gated channel
18
THE END
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