Exam 4: Lecture 4 Flashcards
1
Q
Signal Tranduction Cascade
A
- typically will involve the production of ligand by sending cell
- this molecule will bind to cell surface transmembrane receptor on receiving cell
- activation of receptor will lead to transmission of instructions to nucleus through serial activation of several cytoplasmic factors
- most downstream member of cascade translocates into nucleus where it will physically modify transcription factors (usually via phosphorylation)
2
Q
Phosphate Groups
A
- addition to TFs can sometimes lead to inactivation of protein
- or can lead to activation
3
Q
Morphogens
A
-proteins secreted at one cell to act at a distance to influence the cells that it surrounds.
4
Q
Paracrine Signaling
A
- used by long range signaling gradient
- diffuse past most immediate cell neighbors and will make contact with receptors located further away from sending cell
- some signaling molecules are first generated as larger proteins that can be tethered to surface of sending cell plasma membrane
- in response to cleavage event, biologically active ligand can diffuse away-also signal at both short and long range distances
5
Q
Morphogen Gradient
A
- ligand which is produced and secreted from small population of cells is capable of travelling several cell diameters
- Each receiving cell will express the same number of receptor molecules
- however cell closest to sending cell will have highest number of occupied receptors
- more distant cells have fewer occupied receptors
- gradation in receptor-ligand binding can lead to differential levels of activated transcription factors which influences gene expression
6
Q
Gradient Levels and Transcription
A
- cells that are closest have highest levels of ligand-receptor bound complexes.
- leads to highest level of activated TF and in turn all 3 target genes (A, B, and C) actively transcribed
- intermediate cells have fewer occupied receptors and therefore less activated TFs and only genes B and C transcribed
- far cells have least number of occupied receptors and activated TFs so only gene C is transcribed.
- picture on slide
7
Q
Spatzle
A
- secreted by ventral follicle cells that surround developing Drosophila embryo.
- capture of this ligand by Toll receptor leads to translocation of Dorsal TF into nucleus
- vast majority captured by receptors on ventral cells
- remaining captured by Toll receptors on lateral cells
- dorsal receptors never receive
8
Q
Juxtacrine Signaling
A
- tethered to membrane and are never cleaved or secreted by sending cell
- can only signal to cells directly contacting sending cell
- some cases ligand-receptor complex will be internalized within receiving cell
- other cases simple binding of tethered ligand to transmembrane receptor is sufficient to activate receptor and initiate signal transduction
9
Q
Autocrine Signaling
A
- situations in which diffusible ligand is secreted by ell then binds to cell surface receptors on same side of cell
- leads to biochemical changes within same cells
- cells that respond to its environment and releases proteins into cellular membrane, but only affects itself
10
Q
Intracrine Signaling
A
- ligand or hormone enters cell and goes straight to nucleus without interacting with receptors at cell surface
- once in nucleus, bind to nuclear receptors
- together steroid-receptor complex will bind to DNA and activate/repress transcription of target genes
11
Q
Endocrine
A
-ligand/morphogen is secreted into circulatory system to be carried to distant organ or cell population
12
Q
Determining Ligand Diffusion Distance
A
-see example on slide
13
Q
Mechanism of Receptor Tyrosine Kinase Activity (RTK)
A
- mediates many signal transduction cascades
- prior to signal activation, ligand and receptors not bound to each other
- absence of ligand, receptors exist as monomers within plasma membrane
- binding of ligands and receptors changes conformation of receptor so they can physically interact with each other within plasma membrane
- RTKs form dimer complexes
- dimerization triggers activation of kinase domains located in cytoplasmic sections of receptors
- kinase domain is responsible for adding phosphate groups
- RTKs trans phosphorylate each other at conserved tyrosine amino acids located within cytoplasmic sections of protein
- phosphorylated receptor now active and will stimulate activity of cytoplasmic proteins
14
Q
Mechanism of Receptor Tyrosine Kinase Activity (Cytoplasmic Signaling Cascade)
A
- binding of ligand to RTK leads to dimerization and transphosphorylation of receptor
- leads to activation of cytoplasmic signaling cascade
- first molecule activated is Ras which is a GTPase
- Ras activates cytoplasmic Raf kinase
- Raf kinase phosphorylates and activates MEK
- MEK phosphorylates and activates MAPK
- unphosphorylated MAPK found in cytoplasm and dually phosphorylated version is translocated into nucleus
- after MAPK enters nucleus it will phosphorylate several TFs
- some activators will then promote gene expression
- other receptors inhibit gene expression.
15
Q
RTKs
A
- all RTKs transmit signals to nucleus through Ras/MAPK signaling cascade
- activation of different RTKs will lead to modification of very different transcription factors
- different RTKs can function in different tissues while multiple RTKs can also function within same cell
