Term 1- Lec 7&8- Signal Transduction Flashcards
The 4 categories of cell signaling
Autocrine, Paracrine, Endocrine, and Neuronal
Autocrine signaling
Short distance signaling that is meant for cells that are the same as the signaling cell. (Local distribution of ligand among cell population)
Paracrine signaling
Short distance signaling that is meant for different types of cells from the signaling cell. (Local distribution of ligand among cell population)
Endocrine signaling
Long distance signaling. Utilizes bloodstream to transport ligands long distances.
Contact-dependent signaling
Cells have a ligand attached to the surface which is mirrored by receptors on the target cells.
This signaling limits growth
Contact dependent signaling. This feature is often lost in cancer cells.
Type I Diabetes
Autoimmune. Insulin-producing (ß-pancreatic) cells are exhausted because signal is never received and the cells continue to produce the signal until they cannot anymore/told to quit forever
Type II Diabetes
Insulin is made, but target cells become less responsive. Insulin resistance.
Neuronal signaling
Specialized type of Paracrine signaling. Nerve to non-neuronal target cell. Signaling not meant for many cells and is often only delivered to one.
Long and short distance nerve signal travel occur where respectively?
Nerve signals travel long distances in axons and short distances across synapse.
The two phases of neuronal signaling
- Through the neuron via electric potential.
2. Signal to the target cell via neurotransmitters across synapse. (ie Acetylcholine)
Two mechanisms for Ligand Induced Signaling in cells
- Diffusion across the plasma membrane to activate intracellular receptors. (i.e. Steroid hormones)
- Binding and activation of cell surface receptors. (i.e. Insulin)
How do steroid hormones travel in the blood stream?
They require a transport protein because they are hydrophobic and not soluble.
What are the names of the 5 steroid hormones
- Testosterone
- Estradiol
- Progesterone
- Cortisol
- Aldosterone
In what type of cell and how is Nitric Oxide synthesized?
Arginine is acted on by Nitric Oxide Synthase (eNOS) in the endothelium to make NO
Why can NO only affect it’s surrounding cells?
It has a very short half-life, thus it cannot make it that far.
What is the purpose of NO?
To cause vasodilation
What are the three cell types involved in NO signaling
Nerve terminal, Endothelial cell, and Smooth m. (surrounding the endothelial cell of the blood vessel)
What is nitroglycerin’s role in vasodialtion?
Undergoes chemical conversion into NO, causing dialtion of the blod vessels in the heart.
The two types of transmembrane receptors extracellular ligands bind
- G-protein coupled receptor (GPCR)
2. Receptor tyrosine kinase (RTK)
Ligand binding of GPCR/RTK initiates
Phosphorylation cascades
Phosphate group transfer is what type of modification?
Covalent modification
This type of enzyme forms new phophate bonds
Kinases
This type of enzyme breaks phophate bonds
Phosphotases
Kinase proteins transfer phosphates to what functional groups on which AAs?
The hydroxyl of Serine, Threonine, Tyrosine
Where do kinases transfer the phosphate FROM?
The terminal phosphate of ATP
The 4 targets of Kinases
- Other kinases
- Phosphatases
- Metabolic enzymes
- Transcription factors
The two types of ligands that GPCR and RTK bind are:
- Encoded by genes
2. Produced through a series of enzymatic rxns
Most growth factor bind to:
Receptor Tyrosine Kinase
Molecules that activate their receptor
Agonists
Molecules that interfere with receptor activation by it’s natural ligand
Antagonists
Epinephrine and Glucagon both bind to what type of receptor. What do they affect?
GPCRs. They alter metabolism in the cell
G∂-s
Activates Adenylate Cyclase
G∂-i
Inhibits Adenylate Cyclase
G∂-q
Activates Phospholipas C
Adrenergic receptors
Bind to specific ligands to regulate metabolic processes
The 3 main classes of adrenergic receptors
∂1, ∂2, and ß
What is a ß subunits activity dependent on?
The G∂ proetin it is bound to.
Cholera toxin ribosylates (adds ADP-ribose) what? What happens?
G∂-s. G∂-s cannot hydrolyze GTP, Adenylate cyclase remains active, cAMP continues to be produced
Pertussis toxin ribosylates (adds ADP-ribose) what? What happens?
G∂-i. G∂-i cannot get rid of GDP, Adenylate cyclase activity cannot be produced, cAMP continues to be produced.
cAMP increases the activity of
Protein Kinase A (PKA)
What is the structure of PKA?
2 regulatory subunits and 2 catalytic subunits
How does cAMP activate PKA?
cAMP binds to the regulatory subunits, which release the catalytic units
What can PKA phosphorylate
It can phosphorylate the transcription factor for CREB (cAMP regulatory element binding protein) to regulate gene expression
What enzyme deactivates cAMP, and how?
cAMP Phosphodiesterase. Unbinds the phosphate that makes it cyclic, turning it into low energy AMP
The naming difference between the two types of GPCR pathways
G∂-s: activates Adenylate Cyclase
G∂-q: activates Phopholipase C
What cleaves PIP2, and what is produced?
PIP2 is cleaved by PLC to create DAG (stays in membrane) and IP3.
Role of Ca2+ in PLC pathway
Ca2+ acts as a second messenger. It is released via the IP3 signal, then it binds with PKC to activate it (PKC later connects to DAG at the membrane)
How are cytoplasmic Ca2+ levels lowered?
Ca-ATPase in the ER membrane uses active transport to pump Ca2+ back intot he ER. This shuts down Ca2+ dependent signaling
Calmodulin
Activated when bound to Ca2+. causes conformational changes in other proteins by “squeezing” them. Lacks enzymatic properties
Calmodulin activates
CaM Kinase II.
CaM Kinase activation cycle
- Ca/Calmodulin wrap inactive CaM Kinase !! to activate it.
- CaM Kinase II autophosphorylates
- Once Ca levels drop, calmodulin becoves inavtive and unwraps from CaM Kinase II.
- Phosphate attached to CaM Kinase II keeps the kinase ~50-80% active.
General structure of RTK’s
Extracellular ligand binding site and Intracellular Tyrosine Kinase Domain
Ras is what type of enzyme?
GTPase
Where is Ras found in the cell?
Ras is anchored to the plasma membrane by a covalently attached lipid tail
What stimulates Ras activity?
Guanine exchange factor (GEF) INFLUENCE (doesn’t do the work) GTP binding to Ras
What down regulates Ras?
GTPase activating proteins (GAP) INFLUENCE (doesn’t do the work) the hydrolysis of GTP on Ras
What type of protein is SOS and what recruits it to the membrane
SOS is a GEF. GRB2 recruits SOS so that it can activate Ras.
Enzyme that catalyzes cAMP to AMP
cAMP Phosphodiesterase
