Signaling cell

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Class
Cell Signaling
Prof. Lilian Spencer
Communication through extracellular signal molecules
Cell Signal substance Target cell receptor
E.g:- a.a.
- Peptides
- Proteins
Signal translation: Process of conversion of the extracellular signals in 
cellular responses.
Extracellular 1- Synthesis
Signal steps 2- Release of the signal molecule by cell.
Fig. 13-1 3- Transport of the signal to the target cell.
4- Detection of the signal by the specific receptor.
5- Change of metabolism, by fusion or development.
6- Elimination of the signal
The signaling molecule acts as a ligand, which binds to a structurally 
complementary site on the extracellular or membrane-spanning domains of the 
receptor.
Molecule signal operates across various distance
Endocrine: (hormones) Cells act at distances from the synthesis site of 
hormone.
3 types Paracrine: The signal is released by a cell and only 
affects very close target cells.
Eg. Neuron muscle cell.
Autocrine: Cells respond to substances that release by 
themselves. E.g: Epidermal growth factor .(EGF)
Fig. 20-1.
Receptor proteins exhibit ligand and effector binding specificities
E.g. Acetylcholine Receptor Striated muscle cell: contraction Ca+2
Smooth muscle cell: contraction
Pancreatic acines: exocytosis of 
granules
Epinephrine
or Hepatic cell receptor Synthesis of cAMP
Glucagon (Second messenger)
Types of RECEPTORS:
Three major types of transmembrane receptors:
- Ion channel-bound receptors
- The receptors with enzymes and
- G protein-coupled receptors play a role in signal transduction.
The signal into de cell responses and the process, is termed signal transduction. 
Signal transduction pathways may involve relatively few or many components.
Function of Ligand Modify receptor properties
Transmit signal
G Protein-couple receptor (GPCR)
E.g. Receptors. Visual
Olfatory (Smell)
Gustatory (Taste)
Neurotransmitters receptors
Reptors for hormones
Receptors activate a limited amount of signaling pathways Who will be the curve?
2 Types of cellular signaling
External Signal 1- Changes in activity or function of Specific protein 
2- Changes in the amount of Specific proteins produced by a cell 
Modifications of gene transcription factors.
Receptor proteins exhibit ligand-binding and effector specificity.
The cellular response is determined by the particular receptors it possesses, by 
the signal-transduction pathways they activate
Affected intra-cellular processes
Each receptor binds only a single Signaling molecule or groups closely of related 
molecules Different cellular responses
Fig 13-2
In contrast many signaling molecules bind to multiple types of receptors.
Each receptors Each Activates different intracellular signaling 
pathways.
Eg.
Acetylcholine R. Striated muscle cell Contraction because it 
activates the ion channel 
regulated by ligand
heart muscle contraction GPCR
pancreatic acinar cell exocytosis secretory 
digestive enzimes 
Mutational studies have identified the a.a. in growth hormone and its receptor
Trytophane
The maximum cell response for a molecule signaling may not require 
activation of all receptors
The specificity of a receptor refers to the ability to distinguish substances
closely related.
E.g. Insulin Receptor binds Insulin related by R.
EGF 1 hormone 
Kd = [R] [ L]
______ cte of dissociation
[ RL]
Measures the receptor's affinity for the ligand
A lower Kd major is the affinity of R for L.
Fig. 13-3: Maximum cell response for a ligand (similar to kinetic Enzime)
Receptors are difficult to identify and purify Membrane Prot. are separated by 
non-ionic detergents
Cel 10 -4 Membrane proteins are receptors
50%
80%
18%
They determine the weak binding of a ligand by competition assays with another
Ligand binding to the same receptor with high affinity (Assay with radioactivity)
Increasing [L low affinity] not radioactively labeled competitor
Agonists: Imitate the function of natural Hormone.
Analogues 
Antagonists: They bind the receptor but do not induce a response
Reduce physiological activity
Example of agonist. ISOPROTEROL is attached to the Epinephrine receptor.
Used in tte of asma
Example of antagonist is ALPRENOLOL in decreases the cotraction of the heart
Agonist
Antagonist
Receptors can be purified by affinity techniques or expressed
from cloned genes.
Isolation technology By affinity labeling
+ Radioactive marker
washed
Chemical Agents for Cross-linking
Labeled binding molecule + receptor
Detergent
Ligand's ability binds to Anti-bodies.
AFFINITY
Functional cDNA expression assays (Fig. 13-6)
Intracellular signal transduction:
Intracellular pathways that transduce downstream signals from the activated receptors 
differ in their complexity and mode.
Second Messengers : 
Ligands first messenger + R
Induced intracellular molecules = Second Messengers
Example:cAMP
cGMP
DAG= Diacylglycerol (diacilglicerol) Fig. 13-7
IP3 = Inositol triphosphate (Inositol trifosfato)
Ca+2 = Calcium
IP3DAG
cGMP
cAMP
Intracellular proteins (I.P) RECEPTOR 2 MESSANGERS Response I.P
work on the transduction of signals
Intracelular Prot. GTPase Switch F. GTPase Prot G
Hydrolysis of GTP
guanine nucleotide- change factor
Protein kinasas and Fosfatasas (GEF) release GDP
Classes of GTPase switch proteins P. G trimeric (large) G proteins
P. G monomeric= E.g. Ras
PK (protein-kinasa) Leads to changes in phosphorylation
PK Adds phosphorus to the hydroxyl group Tyrosine
Serine/Threonine
Phosphatase It eliminates phosphate and can act in conjugated form with kinase
Receptor = Cytosolic PK or Phosphatase
Many proteins are substrate for multiple kinases and each phosphorylation modifies the 
activity of a target protein active
inactive
Some receptors and signal transduction proteins are located:
Adapter domains Chemical Synapse Domain PDZ(90a.a)
3 a.a. C-terminal
ser/tre-X-Θ
Fig. 13-9a
Fixed
Actin filaments 
More common is the clustering of receptors
and other membrane-associated signaling proteins to a
particular region of the cell surface
Some Receptors and Signal-Transduction Proteins Are Localized
G Protein–Coupled Receptors That Activate or Inhibit Adenylyl 
Cyclase
(GPCRs) contain seven membrane-spanning regions with their N-terminal segment 
on the exoplasmic face and their C-terminal segment on the cytosolic face of the 
plasma membrane.
Interaction Protein G
Activating a Receptor Induces the production of multiple
Effector protein 2nd messengers with 
different effects
E.g. Degradation of Glycogen
Receptor desensitization High concentration signal 
or
Prolonged expression of a signal
Reducing the receptors by endocytosis
or
Modulation of receptor activity is often the result of receptor phosphorylation.
Prot. G (GPCR) receptor that activates or inhibits adenylyl cyclase.
Contains 7 trans-membrane regions
-N-terminal segment exo-plasmatic
and C-terminal in the cytosol R. hormones
Neurotransmitter
Prot.G Fig 13-11 R. Powered by Light 
G Protein–Coupled Receptors That Activate or Inhibit Adenylyl Cyclase
Adenylyl Cyclase Is Stimulated and Inhibited by Different 
Receptor-Ligand Complexes
prostaglandin
Hepatic cell
Prot. G cAMP PKA active Express Ez to degrade Glycogen
(Glycogen phosphorylase)
Adipose Cell 
Adrenalin PKA active Phosphorylation Catalysis
+ β Adrenergic receptor- and
Prot G activation of Hydrolysis of the 
Phospholipase Triglycerides
Fatty acids + glycerol
Glycogen is regulated by the activation of PKA induced by H. Adrenalin (EPINEPHRYN)
Fig 13-17a
1- H cAMP Activate PKA Glucose1P
Stimulates Glycogen degradation
Inhibits Glycogen synthesis
2- PKA Degrades Glycogen
Activate GPK = glycogen phosphorylasekinase Phosphorylates and activates
Glycogen phosphorylase
Glycogen Metabolism Is Regulated by Hormone-Induced Activation of 
Protein Kinase A
Signal Amplification Commonly Occurs Downstream from Cell-
Surface Receptors
An epinephrine stimulus of this magnitude
generates an intracellular cAMP concentration
of 10 -6 M, an amplification of 104
This cytosolic protein binds to receptors extensively phosphorylated by BARK and 
completely inhibits their interaction with and ability to activate Gs.
FIN