Transcript signal transduction-2014

Signal transmission
and
signal transduction
XIA Qiang, MD & PhD
Department of Physiology
Room 518, Block C, Research Building
School of Medicine, Zijingang Campus
Email: [email protected]
Tel: 88206417 (Undergraduate school),
88208252 (Medical school)
OUTLINE
Intercellular signal transmission
Chemical transmission
Electrical transmission
Signal transduction pathway
Pathways initiated by intracellular receptors
Pathways initiated by plasma membrane receptors
Intercellular signal transmission
Chemical transmission
Chemical signals
Neurotransmitters:
Intercellular signal transmission
Chemical transmission
Chemical signals
Neurotransmitters:
Humoral factors:
 Hormones
 Cytokines
 Bioactivators
Intercellular signal transmission
Chemical transmission
Chemical signals
Neurotransmitters:
Humoral factors:
Gas: NO, CO, etc.
Intercellular signal transmission
Chemical transmission
Chemical signals
Receptors
Membrane receptors
Intracellular receptors
Receptors on the
surface of a cell
are typically
proteins that
span the
membrane
Only Cell A has the
matching receptors
for this chemical
messenger, so it
is the only one
that responds
Cells B & C lack the matching receptors
Therefore are not directly affected by
the signal
Intercellular signal transmission
Electrical transmission
Gap junction
Cardiac Muscle
Low Magnification View
The intercalated disk is made of several types of intercellular
junctions. The gap junction provides a low resistance pathway for
the action potential to spread from cell to cell
Signal transduction pathway
Pathways initiated by intracellular receptors
Pathways initiated by plasma membrane
receptors
This hydrophobic signal
requires a carrier protein
while in the plasma …
… but at the target cell
the signal moves easily
through the membrane
and binds to its receptor
Signal transduction pathway
Pathways initiated by intracellular receptors
Pathways initiated by plasma membrane
receptors (transmembrane signal transduction)
Transmembrane signal transduction
Transmembrane signal transduction
Mediated by G protein-linked receptor
Mediated by enzyme-linked receptor
Mediated by ion channel
Binding of ligands to membrane-spanning receptors
activates diverse response mechanisms
Transmembrane signal transduction
Mediated by G protein-linked receptor
Mediated by enzyme-linked receptor
Mediated by ion channel
The Nobel Prize in Physiology or Medicine 1994
 "G-proteins and the role of these proteins in signal
transduction in cells"
Alfred G. Gilman
Martin Rodbell
The Discovery of G Proteins
Normal Lymphoma Cell
Mutated Lymphoma Cell
Activation and Inactivation of the G Protein
1. The G protein, composed of alpha-, betaand gamma-subunits, in its resting state
with bound GDP.
3. ...with GTP and the G proteins is
activated. The subunits separate.
2. The receptor with bound hormone
activates the G protein and replaces GDP...
4. Some seconds later the GTP, bound to the
alpha-subunit, is hydrolysed to GDP. The
subunits recombine.
G-protein-coupled Receptors
Signaling molecules involved

G protein
 effector

Second
messenger
Protein
 kinase
Main signaling pathways
(1) cAMP-PKA pathway
(2) IP3-Ca2+ pathway
(3) DG-PKC pathway
(4) G protein-ion channel pathway
(1) cAMP-PKA pathway
Gs, Gi
The cyclic AMP second messenger system
Adenylyl cyclase forms cAMP,
a “second messenger”
that activates enzymes
used in cellular responses
The phosphodiesterase
enzymes “terminate” the
second messenger cAMP
The cAMP system rapidly amplifies the response
capacity of cells: here, one “first messenger” led
to the formation of one million product molecules
Cells can respond via
the cAMP pathways
using a diversity
of cAMP-dependent
enzymes, channels,
organelles, contractile
filaments, ion pumps, and
changes in gene expression
(2) IP3-Ca2+ pathway: Gq
(3) DG-PKC pathway: Gq
DAG: diacylglycerol
IP3: inositol 1,4,5-trisphosphate
PIP2: phospholipid phosphatidylinositol 4,5-bisphosphate
This receptor-G-protein complex is linked to and
activates phospholipase C, leading to an increase
in IP3 and DAG, which work together to activate
enzymes and to increase intracellular calcium levels
Click here to play the
Membrane Bound Receptors,
G Proteins,
and Calcium Channels
Flash Animation
(4) G protein-ion channel pathway
Binding of the ligand to the receptor alters the
receptor’s shape, which activates an associated
G-protein, which then activates effector proteins,
i.e., enzyme functions or ion channels
The calcium-calmodulin
system is similar to some of
the cAMP pathways, because
it results in the activation of
protein kinases that can
phosphorylate key proteins
required for cellular responses
The “arachidonic acid cascade” is activated in
inflammation responses; “cox inhibitors” block
cyclooxygenase
Not all responses to
hydrophilic signals
are immediate:
Increases in gene expression
can occur, and the resulting
proteins can increase the
target cells’ response
Eicosanoid: A lipid mediator of inflammation derived from the 20-carbon atom arachidonic acid
(20 in Greek is "eicosa") or a similar fatty acid. The eicosanoids include the prostaglandins,
prostacyclin, thromboxane, and leukotrienes.
Transmembrane signal transduction
Mediated by G protein-linked receptor
Mediated by enzyme-linked receptor
Mediated by ion channel
Binding of the ligand to the receptor alters the
receptor’s shape, which activates its enzyme
function, phosphorylating an intracellular protein
(1) Tyrosine Kinase Receptor
Insulin receptor
Growth factor receptor
Mitogen-activated protein kinase (MAPK)
pathway
•PTK: protein tyrosine kinase
•Ras: G protein. It consists of an a subunit,
b subunit, and g subunit
•MAPKKK: MAPK kinase kinase
•MAPKK: MAPK kinase
•MKP: MAPK phosphatases
•TF: tissue factor
(2) Receptor-associated tyrosine kinase
JAK stands for Janus kinase or
Just Another Kinase
JAK2=Tyrosine protein kinase 2
Binding of the ligand to the receptor alters the
receptor’s shape, which activates an
associated enzyme function, phosphorylating
an intracellular protein
(3) Receptor guanylyl cyclase
Soluble GC
Transmembrane signal transduction
Mediated by G protein-linked receptor
Mediated by enzyme-linked receptor
Mediated by ion channel
Binding of the ligand to the receptor
alters the receptor’s shape, which
then opens (or closes) an ion channel
N2-ACh receptor channel
Any other pathway else?
?
?
Pheromone
Pheromones are
chemicals emitted by
living organisms to send
messages to individuals
of the same species.
The male silk moth bombyx mori (Fig. 1, left) can detect very low quantities of
the sex pheromone bombykol emitted by the female, and at the same time
distinguishes bombykol from many other, often similar, volatile compounds in the
air. A first step of olfaction is the tranfer of bombykol to the pheromone receptor at
the neuronal membrane via the pheromone-binding protein (BmorPBP). Highly
efficient uptake and release kinetics of bombykol at the pheromone binding protein
is essential for olfactory function. However, BmorPBP features a central
hydrophobic binding cavity for bombykol, completely encapsulating the ligand (Fig.
1, right) and the exit/entrance gate for bombykol is not known. Yet, the ligand has
to enter and exit the cavity fast and reversibly.
THANK YOU FOR YOUR
ATTENTION!