Lecture 19: Cell Signaling I Flashcards
What are some examples of Direct Cell Signaling
*Cells are directly touching one another
-Juxtacrine Signaling
-Gap Junctions
Signaling through plasmodesmata
What are some examples of paracrine signaling
autocrine signaling
neuron signaling
paracrine (to another cell signaling)
What is endocrine signaling
through the blood stream to act on the target organ
What are the steps of cellular signaling
- receptor ligand binding
- Signal transduction sometimes via second messengers
- Cellular response
4 changes in gene expression
__________ signaling molecule fits binding site on tis complementary receptor other signals do not fit
specificity
_____________ when enzymes activate enzymes, the number of affected molecules increases geometrically in an enzyme cascade
amplification
____________ proteins with multivalent affinities form diverse signaling complexes from interchangeable parts. Phosphorylation provides reversible points of interaction
modularity
____________ receptor activation triggers a feedback circuit that shits of the receptor or removes its from the cell surface
Desensitization and adaptation
____________ when two signals have opposite effects on the metabolic characteristic such as the concentration of a second messenger X or the membrane potential Vm the regulatory outcome results from the intregrated input from both receptors
integration
_______ when the enzyme that destroys an intracellular message is clustered with the message producer, the message is degraded before it can diffuse to distant points, so the reponse is only local and brief
localized response
________ external ligand (L) binding to receptor (R) activates an intracellular GTP binding receptor protein (G) which regulates an enzyme that generates an intracellular second messenger
G protein coupled receptor
_____________________ ligand binding activates tyrosine kinases activity by autophosphorylation
receptor enzyme
____________ transcription factor T altering gene expression
kinase activités
_____________ channel opens or closes in response to concentration of signal ligand or membrane potential
gated ion channel
_____________ hormone binding allows the receptor to regulate the expression of specific genes
nuclear receptor
What are some disease associated with G protein receptors
depression, cancer, blindness, diabetes
G protein receptors is A plasma membrane receptor with
______________s, an enzyme in the plasma
membrane that generates an
intracellular second messenger, and
a guanosine nucleotide–binding
protein (G protein).
seven transmembrane helical
segment
G-protein cycles
between ________________ forms, an
effector enzyme or ion channel in the
plasma membrane that is regulated
by the activated G protein.
active (GTP-bound) and
inactive (GDP-bound)
What are the steps of epinephrine signaling
- epinephrine binds to specific receptor
- Hormone receptor complex causes the GDP bound to Gsa to be replaced by GTP activating Gas
- activated Gsa separates from GsBy moves to adenyl cycle and activates it. Many GSA subunits may be activated by one occupied receptor
- Adenyl cyclase catalyzes the formation of cAMP
- cAMP activates PKA
- Phosphorylation of cellular proteins by PKA cause the cellular response to epinephrine
- cAMP is degraded reversing the activation of PKA
Gs proteins are __________ via the GTPase switch. Intrinsic GTPaseactivity hydrolyses GTP spontaneously thereby inactivating the protein
Self activating
cAMP as a second messenger activates ____________________
Protein Kinase A
________________ brings every major player in the pathway into close proximity, allows pathway to function as an assembly line complex
A kinase anchoring protein
______________ is another known component of the complex, yet another way to turn off signaling (PP2A slowly rips off the phosphoryl groups that were installed by PKA)
PP2A Protein phosphatase 2A
In terms of terminating GPCR Signaling what are some methods?
- As epinephrine drops below Kd for its receptors, the hormone dissociated from the receptor and the receptor reassumes it inactive conformation
- Hydrolysis of GTP bound to G alpha subunit catalyzed the intgrinsic GTPase activity of G protein
- Remove the second message cAMP is hydrolyzed 5 AMP cyclic nucleotide phosphodiesterase enzyme
- Activation of phosphoprotein phosphatase which hydrolyze phosphorylated SER, The, Tyr residues releasing inorganic phosphates
____________ is a major CA 2+ binding protein in human cells, protein is tropical inactive at low Ca 2+ becomes active at high Ca 2+
Caladium
__________ is a cousin of calmodulin preens t in muscle cells that activates tropomyosin
Troponin
In rod and cone cells, light actives ___________ which activates G protein transducin
Rhodopsin
In the eye:
The freed ____________________ of transduction activates a cGMP phosphodiesterase which lowers cGMP and thus closes cGMP dependent ion channels in the outer segment of the neuron
alpha subunit
In olfactory neurons, olfactory
stimuli, acting through GPCRs and G
proteins, _____________________by activating PLC. They
affect ion channels and thus
membrane potential.
trigger an increase in
[cAMP] by activating adenyl cyclase
or [Ca2+]
________________ have GPCRs that
respond to tastants by altering levels
of cAMP, which changes the
membrane potential by gating ion
channels.
Gustatory neurons
The bacterial toxin that causes cholera is an enzyme that catalyzes transfer of the
____________________________. The G proteins thus modified
fail to respond to normal hormonal stimuli. The pathology of cholera results from
defective regulation of adenylyl cyclase and overproduction of cAMP.
ADP-ribose moiety of NAD+ to an Arg residue of Gs
The pathway of cholera results form the defective regulation of ___________________
adenyl cyclase and overproduction of cAMP
Epinephrine, also called adrenaline, is released
from the adrenal gland and regulates energy
yielding metabolism in muscle, liver, and
adipose tissue. It also serves as a
neurotransmitter in __________________
* Its affinity for its receptor is expressed as a
dissociation constant for the receptor-ligand
complex.
adrenergic neurons.
_______________ is an agonist with affinity higher
than epinephrine. Used for treatment of acute
bradycardia, heart block & shock.
Isoproterenol
________________ an antagonist with extremely high
affinity. Used for treatment of hypertension,
angina, cardiac arrythmia, thyrotoxicosis.
Propanolol
