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COMMUNICATION
Second Messenger
Cyclic Nucleotides • Vision depends on cGMP-gated Na+ channels
(cAMP, cGMP) present in plasma membranes of rods
• When rhodopsin (receptor) is activated by light
(stimulus), rhodopsin interacts with the G
protein transducin
• Activated transdusin interacts with cGMP
phosphodiesterase, which increases eGMP and
causes closing of cGMP- activated Na+
channels and hyperpolarization of
photoreceptor cell
IP3 and DAG • G protein activates agonist –receptor complex,
which then cleaves phosphatidylinositol 4,5-
bisphosphate into IP3 and DAG
• IP3 binds receptors on endoplasmic reticulum,
leading to release of Ca2+ into cyctosol, which
triggers cellular response
• Immunosuppressant drug cyclosporine helps
prevent transplant rejection by blocking this
pathway.
Ca2+ Ca2+ calmodulin complex activates myosin light-
chain kinase (a calmodulin-dependent protein
kinase), which phosphorylates myosin, resulting in
smooth muscle contraction.
Protein Kinases
Protein Kinase • Enzyme activated by second messenger that
phosphorylates proteins on serine or threonine
residues (protein phosphatase is enzyme that
dephosphorylates proteins).
• cAMP-dependent protein kinase phosphorylates
rate-determining enzymes in glycogen metabolism
• Ca2+ stimulates protein kinase C, which stimulates
cell division and is involved in growth of tumor
cells.
Protein Tyrosine Kinase • Membrane receptors that are themselves
protein kinases
• When agonist binds receptor, protein
tyrosine kinase ohosphorylates protein
substrates on tyrosine residues
• Receptors for insulin and those for growth
factors (epidermal growth factor, colony-
stimulating factor, fibrolast growth factor)
are protein tyrosine kinases.
• Uncontrolled protein-tyrosine kinases play
major role in cell transformation and
malignancy
G Proteins
Heterotrimeric • Nucleotide regulatory protein that aids in
translation of signals between cells and helps
modulate intracellular concentrations of second
messengers.
• In active state, acts as GTPase, hydrolyzing GTP
toGDP
• Adenylyl cyclase (enzyme that aids synthesis of
cAMP) and cGMP phosphodiesterase (enzyme
that
breaks down cGMP) are modulated by G proteins.
• Activation of phospholopase A2 by G protein leads
to production of arachidonic acid
Monomeric • Small G protein involved in protein synthesis, cell
proliferation, neoplastic cell transformation and
vesicle transport.
• Ras like G protein regulate cell growth and
differentiation
• Rab-like G protein help target vesicles to
membranes
Intercellular Communication
By Chemical Mediators