Transcript problem set

Chap. 15 Problem 2
Signaling systems are classified based on the distance over which they act.
Endocrine signaling acts over long distances within the organism. Paracrine
signaling acts over a very short distances, for example between neighboring
cells. In autocrine signaling, cells release ligands that bind to their own surface
receptors, modulating activity.
Because growth hormone is synthesized by the pituitary gland in the brain and
travels to the liver by the blood, growth hormone signals via an endocrine
mechanism.
Chap. 15 Problem 3
Receptor 2 has greater affinity for the ligand than Receptor 1 because the Kd
for Receptor 2 (10-9 M) is lower than the Kd for Receptor 1 (10-7 M). The
fraction of receptors that are bound to the ligand when its concentration is
10-8 M can be calculated using the rearranged form of the Kd equation,
[R]/[LR] = Kd/[L].
For Receptor 1, [R]/[LR] = (10-7 M)/(10-8 M) = 10/1 at this concentration of
ligand. The receptor therefore is only about 10% saturated with ligand.
For Receptor 2, [R]/[LR] = (10-9 M)/(10-8 M) = 1/10 at this concentration of
ligand. The receptor therefore is about 90% saturated with ligand.
Chap. 15 Problem 6
The G protein cycle of activity in hormone-stimulated G protein coupled
receptor (GPCR) regulation of effector proteins is summarized in Fig. 15.17
(next slide). The trimeric G protein complex is tethered to the inner leaflet of
the cytoplasmic membrane via lipid anchors attached to the Ga and Gg subunits.
The trimeric GDP-bound form of the G protein is inactive in signaling. The
binding of a hormone to the GPCR triggers a conformational change in the
receptor (Step 1) which promotes its binding to the trimeric G protein (Step 2).
Binding to the activated GPCR triggers exchange of GTP for GDP and activation
of the Ga subunit which dissociates from Gßg (Steps 3 & 4). Ga-GTP then binds
to the effector protein regulating its activity (Step 5). In time (often < 1 min),
GTP is hydrolyzed to GDP and Ga becomes inactive (Step 6). It then recombines
with Gßg.
If a mutation increased the GTPase activity of the Ga subunit, then the subunit
would be active for a shorter time than normal. The activation of the
downstream effector would therefore be reduced.
Chap. 15 Problem 6 (continued)
Chap. 15 Problem 10
(modified)
channels via G proteins. Describe the rhodopsin signal
transduction pathway.
The rhodopsin signal transduction pathway is shown in Fig. 15.23. Light
absorption by rhodopsin triggers GTP/GDP exchange on the transducin (Gat
subunit, and dissociation of this trimeric G protein. Gat-GTP binds to and
activates a cGMP phosphodiesterase, reducing intracellular cGMP level. This
indirectly results in the closing of non-selective Na+/Ca2+ ion channels in the
cytoplasmic membrane and hyperpolarization of the membrane potential. This
results in decreased release of neurotransmitter from the cell.
Chap. 15 Problem 12
In the liver, muscle, and adipose tissue, epinephrine raises cAMP levels through
Gas-GTP activation of adenylyl cyclase. The key target of cAMP is protein
kinase A (PKA) (Fig. 15.29a). Through this point in the epinephrine-cAMP
pathway, the steps of signal transduction are the same in all three tissues.
However, each tissue differs in the downstream targets of PKA, resulting in cell
type-specific responses.
Chap. 15 Problem 15
Phospholipase C (PLC) cleaves the membrane lipid, phosphatidylinositol 4,5bisphosphate (PIP2) to the second messengers, inositol 1,4,5-trisphosphate (IP3)
and diacylglycerol (DAG) (Fig. 15.35). The steps downstream of PLC are
illustrated in Fig. 15.36a. IP3 diffuses from the cytoplasmic membrane to the
ER where it binds to and triggers the opening of IP3-gated Ca2+ channels. The
rise in cytoplasmic [Ca2+] activates calmodulin which in turn activates certain
cytoplasmic kinases, such as glycogen phosphorylase kinase. DAG binds to and
activates the kinase known as protein kinase C (PKC). Cells replenish ER calcium
via ER membrane Ca2+-ATPase pumps that transport calcium back to the ER
lumen. These pumps also transport cytoplasmic calcium outside of the cell.
Extracellular calcium is transported back into the cytoplasm by activation of
store-operated calcium channels in the cytoplasmic membrane. This calcium
ultimately is transported back to the ER lumen by the ER membrane Ca2+ATPase pumps (not shown).