Lecture 5: Cell Signaling - Exam 5 Flashcards
What is activin?
A TGF-beta signaling ligand and can function as a morphogen.
What is a morphogen?
A substance that produces different effects with differing doses.
Big time key concept:
Morphogen = ?
A diffusible molecule that can determine the fate of a cell by its concentration.
Key Concept: It is the combination of the different TFs and associated co-factors on the different CREs that ultimately determines…?
When and where the gene will be expressed.
CRE = ?
Cis regulatory element = can be an enhancer, promoter, and/or repressor.
Morphogen gradients establish?
The spatial position of early gene regulatory networks (GRNs) in most animal species.
Will every transcript make it to a protein in the cell?
No. There are several possible levels of control. One of them being phosphorylation of proteins.
RTK signaling pathway:
Activation of Ras, Raf, and ERK downstream of receptor tyrosine kinases.
Write down to remember.
RTK signaling pathway:
of immediate early genes by ERK.
Write in notebook
The _____ oncogenes contribute to the development of about 50% of all colon cancers, 25% of lung cancer, and 90% of pancreatic cancers.
ras
RTK signaling pathway:
What is the effect of the most common Ras mutation on the signaling pathway?
Sos which binds GEF and activates Ras. Ras then activates the MAPKKK Raf… which activates the MAPKK MEK…. which in turn activates the MAPK ERK. Then P-ERK translocates to the nucleus… where it modulates transcription.
What is an example of super condensed evolution?
The making of the dachshund. FGF4-RTK signaling is messed up and breeding reinforced a mutation.
Describe signal transduction through RTKs.
- Ligand binding
- Aggregation, autophosphorylation and GRB2 binding to receptor.
- Sos recruitment results in exchanges of GTP for GDP in the protein Ras causing activation of Ras.
- Simultaneously, Phospholipase Cy binds to phosphorylated Tyr resides resulting in the cleavage of PIP2 to IP3 and diacylglycerol.
What is a phospholipase?
A class of membrane-associated enzymes that cleave phospholipids just before the phosphate group.
What is PIP2?
Phospholipid phosphatidylinositol 4,5-biphosphate
Describe the PI 3-kinase/Akt pathway.
PI 3-kinase is recruited to activated receptor tyrosine kinases via its SH2 domain.
PI 3-kinase phosphorylates the 3 position of inositol, converting PIP2 to PIP3.
Akt is activated as a result of phosphorylation by two other protein kinases (PDK1 and mTORC2) that also bind PIP3.
Can paracrine signaling be contact independent?
Yes. Wnt Signaling.
Describe the Canonical Wnt Pathway.
Write on paper.
What is Wnt required for?
Posterior development.
What does antibody staining tell you?
Where and when a protein exists in a cell or EC matrix.
What is Delta-Notch signaling?
Very ancient: present in sponges
A simple way to make some cells in a sheet of cells different from the others and form boundaries. Often used to make binary decisions between cells.
Describe the process of notch signaling.
Notch serves as a receptor for direct cell-cell signaling by transmembrane proteins (e.g. Delta) in neighboring cells.
The binding of Delta leads to proteolytic cleavage of Notch by y-secretase.
This releases the Notch intracellular domain, which translocates to the nucleus and interacts with the CSL transcription factor to induce gene expression.
Delta-Notch signaling:
Different ways that it can work, what cells receive the signal?
only adjacent cells will receive the signal.
Delta-Notch signaling:
Lateral Inhibition
1) two cells send similar signals. everyone starts off the same type of cell so they all have the same genes turned on.
2) randomly, one cell starts to send a stronger signal. cell randomly becoming more special than their neighbors.
3) the receiving cell adopts a different fate. cells are so special that they don’t want their neighbors to join, so they tell the surrounding cells that they are touching to stop expressing the same genes.***
-A simple mechanism to choose different cell fates
