Professional Documents
Culture Documents
Cell Signaling PDF
Cell Signaling PDF
• Ligand binds to
receptors in the plasma
membrane, cytoplasm
or nucleus
• Signaling proteins
interact with target
proteins which regulate
cell growth and
division
Cell-to-Cell Communication
Characteristics
• Multiple, hierarchical
steps
• Amplification of the
hormone-receptor binding
event
• Activation of multiple
pathways and regulation of
multiple cellular functions
• Antagonism by constitutive
and regulated feedback
mechanism
Cell-to-Cell Communication
• Secretion of signaling
molecules is cell type
specific
• Ability to respond to
a specific signaling
molecule depends on
the expression of
receptors that bind
the signaling molecule
with high affinity and
specificity
Cell-to-Cell Communication
• Signaling molecules
can act over long or
short distances and
require cell-to-cell
contact or very close
proximity
Contact Dependent Signaling
• Important during
development and in
immune response
Paracrine Signaling
• Usually taken up by
target cells or rapidly
degraded
Autocrine Signaling
• Release of a molecule
that affects the same
cell or other cells of
the same type
Synaptic Signaling
• Hormones are
secreted into the
blood supply and
widely dispersed into
the body
• Permeability is regulated by
cytosolic Ca++, H+, cAMP
& membrane potential
• Depends on the
mechanism of
delivery
2 Basic Classes
1. Plasma Membrane
receptors
2. Nuclear receptors
Plasma
Membrane
Receptors
1. Ion channel linked receptors
2. G protein coupled receptors
(GPCRs)
3. Catalytic receptors
4. "Pseudo receptor" that undergo
regulated intramembrane
proteolysis (RIP)
Ion Channel-linked Receptors
• Interaction is
mediated by
heterotrimeric G
proteins composed
of alpha, beta &
gamma subunits
Catalytic Receptors
• A.k.a enzyme
linked receptors
• Plasma membrane
receptors: intracellular
signaling pathways (2nd
messengers)
• Nuclear receptors:
regulation of gene
expression
2nd Messengers
• Transduces a chemical
signal into an electrical
signal
• G proteins
• heteromeric proteins
composed of 3 subunits
• α, β and γ
• If ligand is absent, G
proteins are inactive
where GDP binds to α
subunit
• Receptor is activated
once ligand is bound and
GTP binds to α subunit
G Protein Coupled Signal
Transduction Pathways
• GTP binding-> dissociation
of α subunit from the complex
& results in release of α
subunit from βγ dimer
• G proteins:
• activated by guanine
nucleotide exchange factors
(GEFs)
• inactivated by GTPase-
accelerating proteins (GAPS)
Termination of GPCR Signal
Transduction Pathways
• Hydrolysis of GTP to GDP and Pi
• G protein coupled to αq
subunit stimulates
phospholipase C -> converts
phosphatidyleinositol 4,5
biphosphate (PIP2) to 1,4,5-
inositol triphosphate (InsP3)
and DAG
• 3 pathways involved:
• Cyclooxygenase pathway
• Lipooxygenase pathway
• Epoxygenase pathway
1st Pathway: Cyclooxygenase (COX)
Pathway
• Cyclooxygenase: facilitate the
metabolism of arachidonic acid to
prostaglandin, thromboxanes &
prostacylins
• Prostaglandin: platelet
aggregation, airway constriction
& inflammation
• Thromboxanes: platelet
aggregation, vasoconstriction
• 5-Lipoxygenase: conversion of
arachidonic acid to leukotrienes
• Epoxygenase: facilitaes
generation of
hydroxyeicosatetrenoic acid
(HETE) and cis-
epoxyeicosatrienoic acid
(EET)
• Phosphodiesterases:
breakdown of cAMP &
cGMP to AMP & GMP
• Phosphatases:
dephosphorylate effector
proteins which were
phosphorylated by
kinases such as PKA
Small Monomeric G Proteins
• Single 20-40 kDa protein;; membrane bound
• 4 Classes of Receptors:
• TGF-Β receptor: 2
subunits
• Insulin receptor
• No intrinsic kinase
activity but associated
with proteins with tyrosine
kinase activity (Src family
& Jannus family (JAK)
• Assembles into
homodimers, heterodimers
or heterotrimers
Nuclear Receptor-Linked Signal
Transduction Pathways
• Subfamilies:
1. Steroid receptors
• Located in cytoplasm
• Glucocorticoids suppress
transcription activator protein-1
(AP-1) & nuclear factor kB (NF-
KB) which reduce inflammation
Nuclear Receptor-Linked Signal
Transduction Pathways
• Located in nucleus