Cell Signaling I (Sept. 11 - Simmons) Flashcards Preview

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Flashcards in Cell Signaling I (Sept. 11 - Simmons) Deck (35):

What two components are necessary to transduce a signal?

1. Signaling molecule
2. Corresponding receptor


What are the types of signaling 5 general types of signaling

1. Autocrine
2. Paracrine
3. Contact dependent
4. Synaptic
5. Endocrine


Describe autocine signaling

Cell secretes its own signaling factors that effects itself


Describe paracrine signaling

Cell secretes signaling molecules that affect cells with receptors only in local area


What is contact dependent signaling?

When a cell usually containing a signaling molecule in its plasma membrane docks/contacts another cell with the receptor and causes the signal to be transduced


Describe synaptic signaling

Usually at the end of axons (affecting other nerves or a target cell). Signaling molecules must diffuse into space and cross a junction in order to bind the receptor. (Neurotransmitters)


What is endocrine signaling?

Systemic signaling - usually occurs when hormones are secreted into bloodstream on a diffuse level. Slow to effect but prolonged. Affects target cells downstream


How is it that cells do not universally respond to signaling molecules the same way?

Each cell contains or may lack specific receptor domains for each signaling molecules ensuring specific responses to different molecules


Describe how cells can use multiple signaling molecules to decide what to do?

Different signaling molecules and their combinations dictates to a cell whether they should grow, divide, differentiate, or undergo apoptosis.
(additive signal transduction)


True/False: A signaling molecule may have different effects depending on the target cell

True. Acetylcholine works in different ways to produce different responses in different tissues. Multiple receptors exist for each signal


Signaling molecules which are found floating throughout the bloodstream are usually ______ and cannot _______ the cell

1. hydrophilic
2. enter


Hydrophobic signaling molecules have to have this when in the blood stream...

What is a carrier protein


What is the most common type of hormone that affects nuclear receptors

Steroid hormones


How do steroid hormones work to elicit an effect in cells?

-Diffusion into cell
-Binding to steroid receptor (transcription factors)
-Activation of said transcription factor
-Induction of primary-response proteins


What are the differences between primary-reponse and secondary-response proteins?

Primary response proteins may either repress primary receptors or go on to turn secondary response genes.
Secondary response proteins are created from primary response protein signals. (referred to as delayed response to hormones)


Nuclear receptor superfamilies all have this motif in common

DNA binding domain


Nuclear signaling receptors usually have a _______ protein at C-terminus and a _______ binding domain.

1. inhibitory
2. ligand


Describe what happens when a ligand binds to a nuclear receptor

-Inhibitory protein released
-Recruitment of coactivator protein
(binds transcription activating domain and ligand)
-Binding to DNA of receptor
-expression of target genes


What are the two classes of cell-surface receptors?

-Ion-coupled channels
-Enzyme-coupled receptors


How do enzyme-coupled receptors work?

Signaling molecule- in form of a dimer binds to receptors
Causes association of transmembrane receptors and either
1. Activation of their catalytic domains
2. Activation of associated protein


G-protein-coupled receptors are a major part of _____ interaction. Over _____% of them bind to these receptors.

1. Drug/medicine
2. 50%


Describe the critical structure of G-protein receptors

-7 transmembrane passes
-Receptor N- terminal domain (usually found glycosylated)
-C terminal loops form phosphorylation and activation domains in cytosol
-Membrane passes arranged in a circular bundle


The three components of the G-protein are:

-alpha subunit
-beta subunit
-gamma subunit


Which subunit binds GTP? What does GTP do?

Alpha subunit - GTP activates G-protein


An activated G-protein USUALLY dissociates into these 2 forms...

Alpha subunit.
Beta/gamma subunit remain associated.


Describe the RGS proteins

Regulators of G-protein Signaling...function as GAPs
These are usually the target proteins which cause hydrolysis of GTP in alpha subunit and cause inactivation


What is one caveat to the dissociation of G-proteins into two forms...

Some G-proteins are already associated with G- protein coupled receptor. GTP does not necessarily cause dissociation of the protein, but dissociation from the RECEPTOR


What are the 3 families of trimeric G-proteins we have become familiar with...what does each do?

-Gs - activates adenylyl cyclase
-Gi - inhibits adenylyl cyclase
-Gq - activates phospholipase C-beta


cAMP is a cyclic molecule that is derived from which molecule?



How does cAMP affect protein kinase A?

Protein kinase A is held inactive by regulatory subunits. Binding of cAMP causes release of PKA


Protein Kinase A phosphorylates these residues (amino acids). What is the general structural motif where this phosphorylation occurs?

-Arg - Arg - X - S/T - Y (hydrophobic)


How does cAMP mediate a variety of responses?

cAMP is a mediator molecule in the pathway from a signaling molecule (hormone) attaching to a G-protein coupled receptor and inducing the desired effect through PKA


What is CREB?

cAMP response element binding protein that is activated by PKA and induces cell transcription (it is a transcription factor)


How does receptor desensitization occur?

Phosphorylation of C-terminal activating loops of GPCR through the kinase (GPCR kinase aka GRK) causes ARRESTIN to bind and inhibit G-protein signal transduction


Describe how V. Cholera works to cause massive diarrhea taking in mind the the mechanism of cAMP and activation of these G-protein receptors

Vibrio cholera secretes exotoxin and enzyme - this enzymes catalyzes the ribosylation of Arg201 of G(alpha)S subunit. This prevents the hydrolysis of GTP to GDP by tuning off GTPase activity in the alpha subunit.
-Increase cAMP
-Increase PKA
-Activation of CFTR (ABC transporter)
-More efflux of Cl-, Na+, and H2O leads to diarrhea.