Download Cell Signaling Mechanisms

Cell Signaling Mechanisms
Learning Objectives
At the end of the lecture student should be able to
understand;
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Describe the Significance of cell signaling
Discuss types of intracellular communication
Explain First and second messengers
Describe Four features of signal transducing system
Describe the activation of second messenger system
Explain the activation of calcium second messenger system
Cell Signaling: Responding to the outside world
 Cells interact with their environment by interpreting
extracellular signals via proteins that span their plasma
membrane called receptors
 Receptors are comprised of extracellular and
intracellular domains
 The extracellular domain relays information about the
outside world to the intracellular domain
Cell Signaling: responding to the outside world
 The intracellular domain then interacts with other
intracellular signaling proteins
 These intracellular signaling proteins further relay the
message to one or more effector proteins
 Effector proteins mediate the appropriate response
 This event is transduced into secondary responses
within the cell that can be divided into four broad
categories:
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ion channel activation,
G-protein activation,
activation of enzyme activity within the cell,
direct activation of transcription
 Some signals to which cell respond
Cell surface receptors
 Signaling molecules include peptide hormones, catecholamines, insulin, growth factors, cytokines, etc
 Binding, and subsequent events, triggers an  or  in the
cytosolic concentration of a
second messenger; or the
activated,bound receptor acts
as a scaffold to recruit and
activate other intracellular
proteins
Intracellular Receptors
 Signaling molecules include steroid hormones,
retinoids,thyroxine, etc
 Receptor-hormone complex acts a transcription factor to
alter transcription of certain genes
Receptor Characteristics
 Participates in transduction of the signal from the external
messenger to some component of the metabolic machinery
 Has at least one additional functional site which is altered by
ligand binding (allosteric site)
 Extracellular ligands are called "first messengers" and the
intracellular mediators are called "second messengers."
Four features of signal transducing system
Advantages
 Each cell is programmed to respond
to specific combinations of signaling
molecules
 Different cells can respond differently
to the same chemical signal
Six general types of signal transducers
Categories
 Peptides or polypeptides - insulin, glucagon, growth
hormone, insulin-like growth factors, vasopressin,
prolactin….
 Glycoproteins - follicle stimulating hormone (FSH), thyroid
stimulating hormone (TSH)…
 Steroids - glucocorticoids (aldosterone, cortisol), steroids
(progesterone, testosterone), retinoic acid…
 Amino acid derivatives - epinephrine, norepinephrine,
thyroxine, triidothyronine
Three largest classes of cell surface receptors
Ion Channel linked receptor
G protein-linked Membrane Receptors
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e.g. Glucagon, Epinephrine and Thrombin as signaling
molecules
Activates a chain of events 
alterations in concentrations
of signaling molecules;
elaborate sets of interacting
molecules that can relay
signals from cell surface to the
nucleus
Components:
Receptor; Transducer (G
protein):
Effector (membrane-bound
enzyme);
Second messenger (e.g. cAMP);
Response (cascade of highly-regulated protein
phosphorylations, etc
Characteristics of G proteins
 G protein is an  trimeric protein which binds guanine
nucleotides
 They function to couple integral membrane receptors to
target membrane-bound enzymes
 They can be considered molecular switches where in
GDP (inactive)  GTP (active) + 
 . The dissociated  subunit expresses GTPase activity.
 Enzyme linked cell surface receptor
 Phospholipase C mechanism
 Hormonal involvement in responses to a stimulus
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