Signal Transduction Flashcards
Contact-dependent signaling molecules
Membrane bound signal molecule does not leave the cell and not secreted
Binds to the receptor of the target cell
Immune response
Synaptic signaling molecule
Can transmit signal in milliseconds to considerable distances (1)
Electrical signals cause the release of neurotransmitters that act on the target cells
Paracrine signaling molecules
Signaling molecule that secretes and acts on nearby cells
Important in inflammation
Endocrine signaling molecules
Signals through blood stream and acts on target cells
Long distances
How long does epinephrine-mediated heart stimulation take?.
Within seconds to minutes
How long does growth-factor mediated cell growth in cell division take?
Hours because it requires expression and synthesis of new proteins
What activates a simple intracellular signaling pathway?
An extracellular signal molecule
Simple intercellular signaling pathway
① reception (specific) → signal binds to receptors
② transduction → signals bind to various proteins in the cell
③response → proteins respond
Messengers of the cell
① first messengers (extracellular → hormones, Gfs, Environmental stimuli)
② second messengers (intracellular → cAMP, cGMP,DAG, IP3
③ effector proteins (cellular and biological responses)
Signals
Proteins
Peptides
Steroids
Amino acids
Light
Fatty acid derivatives
Odor/scent
Sound
Gases
Cell surface receptors
Signaling molecules - water soluble
Receptor location: cell membrane
Ex: G-protein coupled receptor, ion-channel coupled receptor, enzyme-coupled receptors or enzymes with intrinsic activity
Intracellular receptors
Signal molecule lipophilic (hydrophobic) molecules that can diffuse Across the plasma membrane
Receptor location: cytoplasm or nuclear
Ex: receptors for steroid hormones such as estrogen, progesterone, corticosteroids
Intracellular signaling proteins
Molecular switches
Enhance speed efficiency, a specificity of the response
Activated by phosphorylation or GTP binding
Kinases function
Add phosphate groups to proteins that alters the activity, stability and location of the protein
Phosphatases function
Remove phosphate group
GTP - binding proteins
Biochemical switches
Inactive when bound to GDP and active when bound to GTP
Second messengers
Small intracellular nonprotein molecules that regulate the activity of enzymatic and non-enzymatic proteins
Can bind and alter conformation and behavior of selected signaling proteins
Examples of water soluble second messengers that diffuse in cytosol
cAMP
cGMP
and Ca2+
What is an example of a lipid soluble second messenger that diffused into plasma membrane?
DAG (diacyglycerol)
What are the 4 categories of receptors?
1) GPCRs
2) Ion-channel- coupled receptors
3) Receptors with enzymatic activity
4) Nuclear Receptors
What are the largest class of cell surface receptors?
G-protein couple receptors (GPCRs)
G-protein coupled receptors (GPCRs)
Span the plasma membrane 7 times
More than 800 GPCRs in human
Hormones, neurotransmitters, sight, smell and taste use them
50% of modern drugs target them
Guanine Nucleotide Binding Proteins (G Proteins)
A inactive complex of Ga and Gbg
Ga in the inactive complex
Bound to GDP
What does the activation of G-proteins cause?
Dissociated of the Ga and Gbg complex
GDP is switched with GTP
When can G-proteins have intrinsic GTPase activity?
When ‘on’ state and shut themselves off by hydrating their bound GTP to GDP
Ligand-induced activation of effector protein that’s associated with G protein coupled receptors
- Binding of hormone induces a conformational changed in receptor
- Activated receptor binds to Ga subunit
- Binding induces conformational change in Ga; bound GDP disassociates and is replaced by GTP; Ga dissociates from Gbg
- Hormone dissociates from receptor; Ga binds to effector activating it
- Hydrolysis of GTP to GDP causes Ga to dissociate from effetcor and reassociate with Gbg
Adenylate cyclase
Catalyzes the conversion of ATP to cAMP
What does Cyclic AMP dependent protein kinase (PKA) mediate most?
The effects of cyclic AMP
PKA
Serine/Threonine Kinase
2 catalytic subunits and 2 regulatory subunits
cAMP binds to regulatory subunits and causing them to dissociate
Released subunits activate to phosphorylate specific target proteins
How does epinephrine stimulate heart rate?
Rapidly, releasing the proteins already existing
1) It activates G proteins
2) Ga binds to it and activated adenylate cyclase
3) cAMP increases
4) PKA activates
5) intracellular calcium increases and activates contractile and regulatory proteins
6) rate and force of contraction increases
Vasopressin action
Binds and stimulates GPCR resulting in the translocation of a water channel to the membrane in the collecting duct cells of the kidney
