Reece et al., 9 Ed
• Cell to cell communication occurs in all forms of life whether multicellular or unicellular. It is
a universal phenomenon and is accomplished by a relatively small set of signaling molecules.
• Conservation of the signaling processes is further evidence supporting the evolutionary
relatedness and unity of life
• Cell signaling involves the interaction of proteins
How does signaling work?
External signals are converted to responses within the cell
• Signal transduction pathways – a series of steps converting signals on the cell surface into a
specific cellular response
• Many signal transduction pathways have been discovered and studied. Interestingly, signal
transduction pathways in yeast and animal cells are very similar
• Signal transduction pathways also exist in prokaryotes – e.g., quorum sensing – bacteria
secrete small signaling molecules (acylated homoserine lactones,AHL).AHL are used to
sense the local density of similar cells. The bacterial cells can regulate gene expression using
this form of signaling (i.e., density dependent gene regulation).
• Signaling may be local or over long distances
o Local signaling - direct contact via gap junctions or
- direct contact through cell surface transducers and
- local signaling molecules – local regulators such as
growth factors (paracrine signaling) and neurotransmitters
o Long distance signaling - e.g., hormones in plants and
- signaling molecules vary in size and composition: ethylene
(C 2 )4is a plant hormone that regulates growth; insulin
(51 amino acids) is a mammalian hormone that regulates
blood sugar level
I. Stages of Cell Signaling
1) Reception – target cell detects the signaling molecule when it binds to a receptor on the
cell surface or inside the cell.
2) Transduction – The signal molecule binding to receptor changes the receptor protein in
some way. Molecular interactions relay signals from receptors to target
molecules in the cell. Transduction may be a single step but often consists of
a series of different molecules- signal transduction pathway Reece et al., 9 Ed
3) Response – Transduced signal triggers a specific cellular response – ensures cellular
activities occur at the right time and in the proper coordination with the
activities of other cells of the organism. The response may be a variety of
cellular activities, such as catalysis by an enzyme, rearrangement of the
cytoskeleton or activation of specific genes in the nucleus.
II. Reception of signal molecules
• Signaling molecules bind to a receptor molecule. This alters the receptor shape and ability to
transmit the signal.
• Binding is very specific (i.e., signal molecule shape is complementary to binding site on
receptor). Signaling molecules are often referred to as ligands: a molecule that specifically
binds to another, often larger molecule.
i) Receptors in the plasma membrane
• Most receptors are transmembrane proteins found in the plasma membrane that
react with ligands that are water soluble and too large to freely diffuse through the
• When a signal molecule binds to a receptor, the receptors transmit extracellular
signals to the cytosol by changing shape or aggregating
G-protein coupled receptors
• Work with the aid of G-proteins ▯ proteins that bind energy rich GTP
• G-protein coupled receptors have 7 membrane spanning ▯-helices. Loops between
▯-helices form binding sites for ligand and G-proteins
• G-protein coupled receptors systems are widespread and diverse in function
• How do G-protein coupled receptors work?
a) G-protein coupled receptors work together with G-proteins and another
protein, usually an enzyme. G-proteins are bound to cytoplasmic side of
membrane and work as a molecular switch depending on which of two guanine
nucleotides is bound: when GDP is bound to the G-protein it is inactive; when
GTP is bound to the G-protein it is active
b) The G-protein coupled receptor is activated when a signaling molecule
binds to the extracellular side of receptor. The receptor changes shape and its
cytoplasmic side binds an inactive G-protein. The bound G-protein exchanges
GDP for GTP.
c) The active G-protein dissociates from the receptor, diffuses along the
membrane and binds the enzyme – altering the enzymes shape and activity. The
activated enzyme can trigger the next step in the signaling pathway.
d) The G-protein is a GTPase enzyme and hydrolyzes GTP to GDP. This
activity returns the G-protein to its inactive state
Receptor tyrosine kinases Reece et al., 9 Ed
• Consist of an extracellular ligand binding site, a membrane spanning ▯-helix and
cytoplasmic component with tyrosine kinase activity (i.e., phosphorylate tyrosine
residues on a substrate protein).
• Areceptor kinase complex may activate multiple (10 or more) transduction
• How do receptor tyrosine kinases work?
a) Before a signaling molecule binds, receptor tyrosine kinases exist as
inactive monomers (i.e., extracellular ligand binding site, membrane spanning ▯-
helix and intracellular “tail” containing multiple tyrosines.
b) The binding of signal molecules causes two receptor polypeptides to
associate forming a dimer.
c) Dimerization activates the tyrosine kinase; each tyrosine kinase
phosphorylates tyrosine residues on the tail of the other polypeptide – activating
the receptor protein complex.
d) Relay proteins recognize and bind to the activated receptor tyrosine
kinases. The relay proteins undergo a structural change and are activated. The
activated relay proteins can trigger a transduction pathway.
Ligand-gated ion channel receptors
• Aregion of the membrane receptor functions as a gate that opens or closes in
response to ligand binding. Ligand binding changes the receptor shape and this
results in th2+gate+opening or closing. The gate