Signal Transduction Flashcards
Kd =?
(R)(L)/ (RL)
What is signal integration? give an example
multiple different pathways that “converge on the same node” (i.e. two pathways that
result in the same response
calcium released in the muscle as an example:
calcium causes the release of glucose to be used for ATP production, which will fuel
muscle contraction. Additionally, calcium interacts with the proteins in muscle to allow
for the physical contraction to take place.
What is generation of Calcium
released into cytoplasm from endoplasmic reticulum (ER) or extracellular
space
what are effects of calcium - a second messenger
activates both protein kinase C (PKC) and calmodulin (note: calmodulin binds
to and activates proteins ).
generation of Cyclic nucleotides (cAMP, cGMP):
: adenylyl and guanylyl cyclase convert ATP and GTP into cAMP and cGMP
(respectively) via attachment of the 5’ and 3’ carbons through a phosphodiester bond.
effects of second messenger Cyclic nucleotides (cAMP, cGMP):
cAMP activates Protein Kinase A (PKA) ; cGMP activates protein kinase G
(PKG)
generation of Inositol trisphosphate (IP 3) and diacylglycerol (DAG)
activated phospholipase C cleaves
membrane-bound phosphatidylinositol-4,5-bisphosphate
(PIP 2) (please note the cleavage site! Dr. Jones
emphasizes its importance a couple of times in lecture
effects of Inositol trisphosphate (IP 3) and diacylglycerol (DAG)
diffuse away from the membrane into the
cytoplasm and transduce its signal, while DAG remains
membrane-bound and can activate other proteins in the
lipid bilayer
Is small GTP binding proteins like ras second messengers?
no
Ras is GDP-bound. It is activated by guanine exchange
factor (GEF) , which “kicks” the GDP off. Because intracellular [GTP] is ~10x greater
than [GDP], GTP binds the protein.
what are the three subunits of Heterotrimeric G proteins their targets and effects
i. G s s timulates adenylyl cyclase
ii. G i i nhibits adenylyl cyclase
iii. G q
(“q” for the quirky one) activates PLC
What are two examples of G protein coupled receptors?
cAMP and IP3 and DAG
which receptor interacts with heterotrimeric G protein on the cytoplasmic side of the membrane.
G protein coupled receptors
what is cAMP
the G salpha subunit dissociates when the receptor binds its ligand to activate
adenylyl cyclase, and the resulting cAMP activates PKA (e.g. beta-adrenergic
receptor
what activates IP3 and DAG
PLC then IP 3 activates a channel on the ER which increases
[Ca 2+ ] in the cell, activating calmodulin (which will also activate other proteins!) and
PKC.
what are receptor tyrosine kinases (RTKs)
membrane-spanning receptors dimerize upon ligand binding,
and they undergo activation by auto-phosphorylation on
tyrosine residues
what is bound by associated adaptor molecules ,
which set off a signaling cascade.
phosphotyrosines
whats an example of receptor tyrosine kinase?
insulin receptor
describe Receptor Guanulyl cyclases?
, these receptors will dimerize upon
ligand binding, activating guanylyl cyclase on the cytoplasmic membrane. The resultant cGMP
goes on to activate PKG , initiating downstream effects. These receptors are primarily involved
in body fluid level maintenance . Another variant of this receptor resides wholly in the
cytoplasm , and this is the nitrous oxide (NO) receptor. It is capable of remaining in the
cytoplasm because NO can diffuse across the membrane , therefore no extracellular receptor is
needed.
what are adhesion receptors (integrins)
these receptors span the membrane, but they are unique
because they exhibit outside-in signaling (contact with ECM) and inside-out signaling
(interaction on the cytoplasmic membrane with the talin protein).
what are the three different conformations of integrins
a. Low affinity : neither type of signaling present
b. Intermediate affinity : only one type of signaling present
c. High affinity : both types of signaling present
which receptor do platelets make use of its high affinity conformation? in order to form clots
adhesion receptors integrins
what are notch receptors
: the ligand for this receptor is a cell surface protein from another cell (known
as the instructing cell )
what receptors are crucial for mediating cell - cell interactions
notch receptors
true or false
notch receptor undergoes
intramembrane cleavage, and the cytosolic portion of the receptor diffuses away from the
membrane and travels to the nucleus to act as a transcription factor .
True
what are nuclear receptors
these are crucial for the signaling mediated by fat-soluble hormones (i.e.
can diffuse through the cell membrane).
what are two types of nuclear receptors
Type I receptors live in
the cytoplasm and they travel to the nucleus where they influence transcription. Type II receptors live in the nucleus , and sometimes on the target DNA itself, where they also influence
transcription.
true or false a single ligand-receptor interaction can cause a relatively large response
true
What are the reactions catalyzed by both adenylyl cyclase and PLC? (answer at the end of
the noteset)
adenylyl cyclase converts ATP into cAMP . PLC cleaves PIP 2
, forming IP 3
(diffuses freely through the cytoplasm) and DAG (remains membrane-bound).
