Cell Signaling Flashcards
Types of intercellular signals
Endocrine, paracrine, autocrine, neuronal, and contact
Endocrine
Cell sends signal into the blood stream to act on something that is far away (hormones, insulin, epinephrine, etc…)
Autocrine
Act on the same cell that makes them (growth factors and eicosanoids)
Paracrine
Acts on adjacent/nearby cells (neurotransmitters, growth factors, nitric oxide)
Neuronal Signaling
Synaptic signaling with neurotransmitters
Contact signaling
Signaling between cells that are in direct contact
Specificity
In regards to intercellular systems, a signal molecule is highly specific for its own receptor
Amplification
When enzymes activate other enzymes there is an enzyme cascade
Desensitization/activation
Receptor activation triggers a feedback circuit that shuts off the receptor or removes it from the cell surface
Integration
When two signals have opposite effects on a metabolic characteristic the outcome is integrated output from both. (E.g., if one increase the concentration and another decrease it, the response will be a mixture of the two)
What is the only intracellular receptor that is not on the surface of the cell?
steroid receptor which is in the nucleus, allowing it to roulade the expression of specific genes.
What is the general mechanism for hormone molecules?
They are hydrophobic (lipophilc) and work by inducing gene expression at the level of DNA transcription.
Gated Ion Channel
Receptor linked to ligand or voltage-gated ion channel. Binding of neurotransmitter will make the channel open, resulting in ions moving through the channel.
What are some examples of gated ion channels?
Nicotinic ACh receptors in the muscles and nerve or GABA and glycine in the CNS
Receptor Enzyme (catalytic receptor)
Extra cellular receptor with intracellular tyrosine kinase activity.
Insulin Receptor
Insulin receptor is a tyrosine kinase enzyme in which the binding of a ligand leads to ATP cleavage and the activation of the tyrosine kinase. This can lead to the stimulation of GLUT-4, stimulation of protein synthesis, and induction/repression of genes.
Examples of second messengers
cAMO, IP3, DAG, Ca, cGMP, NO
If the stimuli is epinephrine/norepinephrine, what is the system?
Epi is received by B-adrenergic receptor which activates the adenylate cyclase system
What are the steps in the adenylate cyclase system?
1) Molecule binds
2) GDP on Gs (alpha) is replaced by GTP activating it
3) complex splits up and Gsalpha moves over and activates adenylate cyclase
4) adenylate cycle forms cAMP
5) cAMP activates PKA (enzyme)
6) PKA phosphorylase proteins leading to response
7) cAMP is degraded
Why is the action of the G-protein short lived?
There is an inborn GTPase activity that hydrolysis GTP back to GDP turning off the system. Can self regulate.
What terminates the effect of cAMP?
Phosphodiesterase hydrolysis cAMP to AMP
What will inhibit phosphodiesterase?
Caffeine and theophylline
What inactivates GTP-ase activity?
ADP ribosylation of the G alpha
How does cholera and E.coli work?
They both ADP-ribosylate Gs-alpha resulting in continuously active Gs-alpha
How foes the pertussis toxin work?
ADP ribosylates Gi-alpha resulting in a continuously inactive Gi-alpha
Phosphoinositide System
1) Gqa activates phospholipase C
2) PLS leaves PIP2 into IP3 and DAG
3) IP3 causes Ca to be released from the ER
4) DAG activates membrane bound protein kinase C
5) Protein Kinase C pohosphrylates proteins resulting in cellular responses
What does protein kinase C need for maximal activity?
DAG, Calcium, and phospholipids
CGMP
Acts as a specialized messenger in smooth muscle relaxation, platelet aggregation, and the visual system. Not associated with G-proteins
Nitric Oxide
Synthesized in endothelial cells and diffused to vascular smooth muscle where it activates cytosolic guanylate cyclase which causes smooth muscle relaxation. Considered a vasodilator
What second messengers are involved in vasodilation?
IP3, Ca, NO, cGMP
