Small Group Discussion 03 Physiology of Signal Transduction

1. Classify the following receptors as to type (intracellular receptor – nuclear or cytoplasmic or plasma
membrane receptors). Briefly describe the signal transduction pathway involved in each.
a. Tyrosine kinase receptor

• Plasma membrane receptor

• Ligand binding of Y kinase à Conformational change à Phosphorylation of the Y group of the
protein (autophosphorylation) à Phosphotyrosine serves as a docking site for cytoplasmic protein
à Bound docking protein bind à Activation of other proteins which activate more signaling
pathways à Cascade of protein activation à Cellular response

b. Ligand-gated ion channels

• Plasma membrane receptor

• When ligand binds to the channel receptors, the pore of the channel opens à allowing ions through
the channel
• When the ligand dissociates, the pore closes

c. Steroid hormone (glucocorticoid, thyroid hormones) receptor

• Intracellular receptor (nuclear)

• Because of their hydrophobic character, the steroid hormones and thyroid hormones are able to
enter cells by diffusing across the plasma membrane. Once inside, they bind to intracellular
receptors that are expressed by the hormonally responsive target cells. These receptors which are
members of a family of proteins (steroid receptor superfamily) are transcription factors that contain
related domains for ligand binding, DNA binding, and transcriptional activation. Ligand binding
regulates their function as activators or repressors of their target genes. So, the steroid hormones
and related molecules directly regulate gene expression.

d. G-protein coupled receptor

• Plasma membrane receptors

• G-protein is attached to alpha (which binds and hydrolyzes GTP), beta, and gamma (stable, non-
covalent link) subunits
• GTP: Active; GDP: Inactive
• GDP à GTP
• GTP dissociates into two components (alpha & beta and gamma)
• Ligand à Receptor activation leads to G-protein à Alpha activates effector protein à Second
messenger à Protein Kinase à Downstream proteins

cAMP cGMP IP3/DAG Arachidonic Acid

G-protein type Gs, Gi Gt Gq
Effector Protein Adenylyl Cyclase Phosphodiesterase Phopholipase C Phospholipase A
nd
2 Messenger cAMP cGMP IP3/DAG Arachidonic Acid
Protein Kinase pKA pKG pKC Prostacyclin,
Ca-Calmodulin Thromboxane,
dependent kinase Prostaglandin
Leukotrienes
ETE

e. Receptor bound to janus kinases

• Plasma membrane receptor

• JAKs (located in separate cytoplasmic kinase)
• Ligand binds à Conformational change à Activation of the attached JAK à JAK phosphorylates
target protein to act as transcription factors that will lead to synthesis of new proteins à Activation
of downstream proteins à Cascade of protein activation à Cellular response

SBA | A 20/21
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 Small Group Discussion 03 Physiology of Signal Transduction

2. Illustrate the G-protein signal transduction pathway involved in the administration of epinephrine to
revive a patient who went into cardiac arrest.

3. Explain what is receptor down regulation and upregulation. Explain if receptor upregulation or
downregulation is manifested in the following scenario:

• Down regulation is an adaptation of the cell wherein the total number of plasma membrane
receptors is diminished due to a chronic high concentration of its messenger.
• Up regulation is an adaptation of the cell wherein the total number of plasma membrane receptors
is increased due to a chronic low concentration of the messenger.

a. Laboratory mice exhibited increased hypoglycemic response to exogenous insulin while being
maintained on lower fasting glucose concentration.

Chronic low glucose levels of the mice will induce the up regulation of insulin receptors of the cells.
They exhibited increased hypoglycemic response to exogenous insulin because there were too many
insulin receptors present. If there were many insulin receptors, they will bind all the insulin they can get.
Insulin is a hormone that binds to the cellular glucose receptors and opens them up, allowing glucose to
enter the cell. The spike of insulin levels induced hypoglycemia, like what happened to the mice.

b. A 25-year old employee self-medicated with an opioid analgesic drug to relieve “chronic fatigue
and pain.” He was noted to require increasing doses of the opioid drug with time.

Opioid drugs work by binding to opioid receptors in the brain, spinal cord, and other areas of the
body. They reduce the sending of pain messages to the brain and reduce feelings of pain Opioids are used
to treat moderate to severe pain that may not respond well to other pain medications. The patient is required
to take increasing does of the drug over time because the receptors will undergo down regulation.
Continuous intake of the drug will increase its concentration in the synapses, forcing the cells to
phagocytose some of its receptors because it perceives the environment with high concentration of opioid
messengers as normal. If the patient does not increase the dose after some time, he will experience less
effects from the drug.

SBA | A 20/21
AM+DG
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