2C- Cell Signaling Flashcards
What are chemical messengers?
substances that transmit messages between cells
What is a general sequence of chemical messenger action?
chemical messenger secreted by a cell in response to a stimulus –> diffuses through blood or EC fluid to the target cell –> receptor binds to it –> binding of the messenger to the R elicits a response –> signal ceases and is terminated
What are the events of a chemical synapse?
How does Myathenia gravis affect cell signalling?
It’s an autoimmune disease where the body makes antibodies against the NmAchR.
Once they bind to the R they don’t allow Ach to bind, thereby creating muscle weakness.
What are the differences between endocrine, paracrine and autocrine messengers?
Endocrine - secreted by a cell into the blood and aacts on target cells a distance away
Paracrine- secreted by a cell and acts on neighboring cells. This is like the Ach synapse.
Autocrine- secreted chemicals from 1 cell act on the same cell
What are the 2 major messengers of the nervous system?
Neurotransmitters- nitrogen containing molecules that can be AA’s or derivatives of AA’s.
Neuropeptides- small peptides secreted by neurons that act as neurotransmitters at synaptic junctions or are secreted into the blood as neurohormones.
What are the 4 major types of hormones?
Polypeptide hormones- like insulin
Catecholamines- like epinephrine
Steroid hormones- derived from cholesterol
Thyroid hormone- derived from Tyrosine
What are cytokines?
They are messengers of the immune system
Small proteins that regulate a network of responses designed to kill invading microorganisms
What are eicosanoids?
They control cellular function in response to injury
All derived from arachidonic acid
Almost every cell in the body contains them and act in mainly paracrine or autocrine functions.
What is the mechanism of membrane receptors?
They have extracellular binding domains
They are typically polar molecules that cannot travel across the membrane
They bind to a cell surface receptor and elicit an intracellular response
Catecholamines fall into this category
What is the mechanism of cytoplasmic receptor action?
They are lipid soluble, so they pass through the lipid bilayer
bind to a cytoplasmic R –> R goes through a conformational change –> dissociates from the heat-shock protein –> receptors dimerize –> travels to the nucleus –> acts as a transcription factor on the hormone response element of DNA
What is the mechanism of nuclear receptors?
The lipophilic messenger binds to the R on DNA and changes its activity anmd its ability to associate with or dissociate from DNA
What is the mechanism of ion-channel receptors?
These work like the NmAchR’s discussed before
Signal transduction consists of conformational change when the ligand binds –> opens –> allows ions to flow through
What is the mechanism of kinase receptors?
protein kinases transfer a phosphate group from ATP to the hydroxyl group of a specific amino acid side chain in the protein
basically, when the L binds to the R, the intracellular portion of the R is a kinase and is activated
The kinase then phosphorylates AA’s, proteins or itself.
What is the mechanism of heptahelical receptors?
They contain 7 transmembrane helices
Most common type of plasma receptor
work through 2nd messengers such as cAMP
What is the general mechanism of tyrosine kinase receptors?
exist as monomers with a single membrane spanning helix –> 1 L binds 2 R’s –> R’s dimerize –> intracellular tyrosine kinase phosphorylate each other on certain Tyr residues –> form binding sites for signal transducer proteins
Explain the pathway of the RAS/MAP kinase
Go through the pathway of the insulin receptor and its signal transduction
the insulin tyrosine kinase R exists as a dimer –> insulin binds –> R’s autophosphorylate –> insulin receptor substrate binds and is phosphorylated –> PI3K binds and is activated, SH2 binds and RAS/MAP is activated, PLCý binds and is activated
PI3K activates PKB
What are the steps of the Gs pathway?
What are the steps of the Gq pathway?
- Describe the two forms of guanylate cyclase that can be activated to cause vasodilation. Explain how NO can stimulate this pathway.
-Membrane bound guanylly cyclase receptors convert GTP to second messenger 3’,5’-cyclic GMP (analogous to cAMP). These receptors directly make cGMP in response to binding the appropriate ligand (unlike heptahelical receptors which need G protein singling to adenylyl cyclase to produce cAMP). CGMP is degraded by membrane-bound phosphodiesterase (target of some drugs). Elevated cGMP activates protein kinase G which then phosphorylates target proteins to propagate the response.
-A soluble form of guanylyl cyclase is located in the cytoplasm is receptor for the nitric
oxide neurotransmitter/neurohormone. NO is a lipophilic gas that is able to diffuse into
the cell and is an exception to the rule the intracellular receptors are Gene transcription factors.
-GMP elevating drugs have been used in humans to treat a variety of disorders, such
as angina pectoris (glycerol trinitrate decomposes to NO, which activates a guanylyl
cyclase),heart failure (using nesiritide,which is synthetic BETA natriuretic
peptide,a ligand for activation of a guanylyl cyclase receptor),and erectile dysfunction (through
drugs that inhibit a cGMP phosphodiesterase, such as sildenafil).
