Test 3: Signal Transduction Flashcards
Why is signal transduction pathway used?
PM separates the outside signals from inside the cell
Time categories of Signal Transduction Pathway (STP) are (2). Describe what they modify and how long they take.
- Slow; minutes~hours; activate transcription, translation and targeting
- Fast; seconds~minutes; proteins (pre-made) is modified and the nucleus is not involved.
2 examples of what fast STP do
- Phosphorylate/dephosphorylate
2. Degrade proteins
4 Categories of Sginaling is based on…
how far it travels and its origin
4 Categories of Signaling are…
- Autocrine:
- Paracrine:
- Endocrine
- Direct Contact
Autocrine: Autocrine Signaling is…
Self-self or self-same tissue nearby; used in development to go down a common developmental pathway; “community effect”
Paracrine: Paracrine Signaling is…
Self-diff tissue nearby;
Paracrine: Challenge with this is that… 3 ways to counteract problem
Must ensure signal does not diffuse by..
- Using enzyme to degrade signals
- Immobilizing signal in “sticky” ECM
- Rapidly reabsorbing signal
Endocrine: Endocrine Signaling is…
Cell to cell over long distance; - [ ] b/c signal diffuses throughout whole body; slow b/c long distance
Direct Contact: Direct Contact Signaling is…
2 cells physically interacting with each other as the signal is bound to the cell that is signaling; no diffusion
T-cell activation uses multiple types of signaling. Describe the 3 types.
- Antigen-bearing cells interacts with Helper T-cells via DIRECT CONTACT Signaling
- Helper T-cell release signal and causes ABC to release IL-1 via PARACRINE Signaling
- IL-1 activates T-cell and makes it release IL-2 to activate itself to lead proliferation of more T-cells via AUTOCRINE signaling
The 5 parts of a Signaling Pathways are…
- Specific Signals
- Specific Response
- Amplification
- Reset
- Fine-Tuning
T/F: Specific Response means that a single signal has the same effect throughout the body. Why?
False– Specific reponse to a specific signal WITHIN A SINGLE CELL TYPE due to CELL-TYPE SPECIFIC RECEPTORS. (i.e. Acetylcholine/”fight-or-flight” causes cardiac muscle to relax, salivar gland to secrete, and skeletal muscle to contract.)
Why is specificity of response to specific signal important?
B/c cell is constantly bathed in different signals and must differentiate 1 signal from another by receptor
The classes of signals are…
- Steroid Hormones
- Gases
- Amino Acids
- Eicosanoids
- Polypeptides and Proteins
Steroid Hormone Signals: What are they? What do they effect? Examples?
Made of cholesterol and hence hydrophobic; binds to intracellular receptors to activate TRANSCRIPTION; cortisol, progesterone, testosterone
Gases Signals: What is an example of it? What does it do?
NO smooth muscle relaxant; relaxes blood vessel and increases blood flow; treats angina, pain from constriction of blood vessel
Amino Acid Derivative Signals: What are they? Examples?
NT and hormones; glutamine, histomine, acetylcholine
Eicosanoids: Drivitive of…? Example and its purpose.
Fatty acids; i.e. asprin targetting smooth muscle contractions that lead to clots, pains, and inflammation
Polypeptide & Protein Signals: Involved in…? Examples?
Involved in cell division, differentiation & immune response; insulin, endorphin & epidermal growth factor
Four types of Receptors Exist. They are…
- Steroid Hormone Receptors
- Ion-Channeling Receptors
- G-protein Linked Receptors
- Enzyme-Linked Receptors
Steroid Hormone Receptors: Intra/Extracellular? What speed response? How does it work? What does it ultimately change?
Intracellular receptor; slow because; Cortisol passes through PM, binds to Receptor, enters nucleus and activates Transcription after binding to DNA; Gene expression
Steroid Hormone Receptors: have two parts. They are…
- Binding sites to receptor
2. Binding sites to DNA
Ion-Channeling Receptors: Intra/Extra? What speed response? How does it work? What does it ultimately change?
Extracellular; fast; ligand binds to receptor and channel opens, which opens/shuts ion channel and causes rapid change in efflux/influx of ions; membrane potential
T/F: Ion-Channeling Receptor is always a channel
F: can also be bound to a channel
G-Protein Linked Receptor: Intra/Extra? What speed response? How does it work? What does it ultimately change?
Extra; fast OR slow depending on the enzyme’s activity; ligand binds to receptor and G-protein is activated as a result, another enzyme is activated; Enzyme activity (VARIES)
Enzyme-Linked Receptor: Intra/Extra? What speed response? How does it work? What does it ultimately change?
Intra; fast OR slow depending on the enzyme’s activity; ligand binds to receptor and this activated an enzyme, (1) the receptor itself can be an enzyme that is activated (dimer ligand) or (2) the receptor can be associated with an activated enzyme; Enzyme activity (VARIES)
Enzyme-Linked Receptor: What is the enzyme usually? Usual Purpose?
Protein kinases or phosphatases; growth factors (+ cell size by elongating interphase) or mitogens (+ division by activating mitosis)
Enzyme-Linked Receptor: Tyrosine Kinase: Receptor has two sites of activity. Where and what do they do?
- Extracellular site binds to dimer ligand
2. Intracellular site (TYROSINE KINASE DOMAIN) is a kinase
Enzyme-Linked Receptor: Tyrosine Kinase: 1. Receptor binds to dimer ligand. This causes…
The inactive receptor to come together and be activated as a kinase.
Enzyme-Linked Receptor: Tyrosine Kinase: 2. Activated kinase does… What does it now serve as?
self-phosphorylates, tyrosine on the receptor is now phosphorylated; phosphorylated tyrosine is now a “docking site” for signal molecule
Enzyme-Linked Receptor: Tyrosine Kinase: 3. Explain docking.
Phosphorylated tyrosine on the receptor binds to and hence recruits intracellular signals to PM (b/c the receptor is so close to PM). These bound signaling proteins are enzymes (phospholipase C), kinases, or, in this case, ADAPTOR PROTEINS (that bring other molecules and proteins).
Enzyme-Linked Receptor: Tyrosine Kinase: Docking step is also a RESET point. Why?
The receptor-phosphorylated tyrosine-intracellular signal complex can be deactivated by dephosphorylase; RESET means that all signals die off at this point
Enzyme-Linked Receptor: Tyrosine Kinase: 4. Ras Activation. Explain.
The adaptor protein recruits Ras-activating protein (Guanine Exchange Factor, or GEF), which changes inactive Ras-GDP protein to active Ras-GTP protein by exchanging Guanine. (Surprise!!!!)
Enzyme-Linked Receptor: Tyrosine Kinase: GEF can be undone with…
GAP, or GTPase Activating Protein. GTPase hydrolyzes GTP into GDP
Enzyme-Linked Receptor: Tyrosine Kinase: 4. Ras Activation is a Point of Amplication. Explain.
1 GEF activates many ras protein because it is an enzyme capable of exchanging many GDP with GTP.
Enzyme-Linked Receptor: Tyrosine Kinase: 5. MAP-Kinase-Kinase-Kinase. Explain.
- Active Ras-GTP activates MAP-Kinase-Kinase-Kinase, which phosphorylates (while converting ATP into ADP)
- MAP-Kinase-Kinase, MAP-Kinase-Kinase-P phosphorylates (while converting ATP into ADP) MAP-Kinase
- MAP-Kinase-P-P activates proteins (while converting ATP into ADP)
- Proteins can change protein or gene expression (fast or slow effect)
Enzyme-Linked Receptor: Tyrosine Kinase: 5. MAP-Kinase-Kinase-Kinase is a Point of Reset and a Point of Fine Tuning. Explain.
GAP can convert active Ras-GTP into inactive Ras-GDP. This can entirely dismantle the signaling system or decrease the signal depending on [GAP]
Enzyme-Linked Receptor: Tyrosine Kinase: 5. MAP-Kinase-Kinase-Kinase is a point of Amplication. Explain.
All enzyms can work many substrates; 1 MAP-kinase-kinase-kinase can phosphorylate many MAP-kinase-kinase, and 1 MAP-kinase-kinase can phosphyrlate many MAP-kinases, and 1 MAP-kinase can phosphorylate many proteins.
Heterotrimeric G-Protein-Linked Receptors: They are another example of signaling. The receptor is linked to a G-protein, which is made up of 3 proteins. What are they? What do they do?
α, β, γ
α is GDP/GTP-linked, which means that
Signal Cross-talk is required because…
cell gets multiple signals and must integrate signals to make sure tehy are correct
Signal Crosstalk: (a) 2 receptors, 2 ATP hydrolysis, 1 target enzyme to be dephosphorylated verses (b) 2 receptors, 2 ATP hydrolysis, 2 target enzyme to be dephosphorylated that form a complex. Difference?
(a) cmust have both signals active for enzyme to work
(b) a single subunit can still be active regardless
Signal Adaptation: Works by…
delayed - feedback; response modifies the effect signal has on further response
Signal Adaptation: 3 Mechanisms. Fast? Slow?
- Receptor Downregulation - Fast
- Receptor Phospohrylation - Fast
- Change in expression of gene for signaling proteins - Slow
Signal Adaptation: Receptor Downregulaion. What is it?
Receptor internalized (endocytosed) to remove it from cell surface available for binding
Signal Adaptation: Receptor Phosphorylation. What is it? 3 ways it works
P-receptor has - affinity for lignad, hence requires + ligand for response; P-receptor has - affinity for G-protein; P-receptor binds to an inhibitory protein
Signal Adaptation: Change in expression. How does it work? Use Morphine as example. What does Morphine do normally? Why does this backfire?
Morphine binds to inhibitory G-protein (G:α:i) to deactivate AC, which - cAMP, which -pKA, which decreases pain signaling; Backfire because cell upregulates expression of AC and PKA (proteins) to compensate.
Signal Adaptation: Change in expression. 2 ways it backfires
- greater response to smaller pain
2. more morphine required to inhibit extra AC and PKA
