Lecture 5: Cell Signaling - Exam 5

Question 1

What is activin?

Answer 1

A TGF-beta signaling ligand and can function as a morphogen.

Question 2

What is a morphogen?

Answer 2

A substance that produces different effects with differing doses.

Question 3

Big time key concept:
Morphogen = ?

Answer 3

A diffusible molecule that can determine the fate of a cell by its concentration.

Question 4

Key Concept: It is the combination of the different TFs and associated co-factors on the different CREs that ultimately determines…?

Answer 4

When and where the gene will be expressed.

Question 5

CRE = ?

Answer 5

Cis regulatory element = can be an enhancer, promoter, and/or repressor.

Question 6

Morphogen gradients establish?

Answer 6

The spatial position of early gene regulatory networks (GRNs) in most animal species.

Question 7

Will every transcript make it to a protein in the cell?

Answer 7

No. There are several possible levels of control. One of them being phosphorylation of proteins.

Question 8

RTK signaling pathway:
Activation of Ras, Raf, and ERK downstream of receptor tyrosine kinases.

Answer 8

Write down to remember.

Question 9

RTK signaling pathway:
of immediate early genes by ERK.

Answer 9

Write in notebook

Question 10

The _____ oncogenes contribute to the development of about 50% of all colon cancers, 25% of lung cancer, and 90% of pancreatic cancers.

Answer 10

ras

Question 11

RTK signaling pathway:
What is the effect of the most common Ras mutation on the signaling pathway?

Answer 11

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.

Question 12

What is an example of super condensed evolution?

Answer 12

The making of the dachshund. FGF4-RTK signaling is messed up and breeding reinforced a mutation.

Question 13

Describe signal transduction through RTKs.

Answer 13

1. Ligand binding
2. Aggregation, autophosphorylation and GRB2 binding to receptor.
3. Sos recruitment results in exchanges of GTP for GDP in the protein Ras causing activation of Ras.
4. Simultaneously, Phospholipase Cy binds to phosphorylated Tyr resides resulting in the cleavage of PIP2 to IP3 and diacylglycerol.

Question 14

What is a phospholipase?

Answer 14

A class of membrane-associated enzymes that cleave phospholipids just before the phosphate group.

Question 15

What is PIP2?

Answer 15

Phospholipid phosphatidylinositol 4,5-biphosphate

Question 16

Describe the PI 3-kinase/Akt pathway.

Answer 16

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.

Question 17

Can paracrine signaling be contact independent?

Answer 17

Yes. Wnt Signaling.

Question 18

Describe the Canonical Wnt Pathway.

Answer 18

Write on paper.

Question 19

What is Wnt required for?

Answer 19

Posterior development.

Question 20

What does antibody staining tell you?

Answer 20

Where and when a protein exists in a cell or EC matrix.

Question 21

What is Delta-Notch signaling?

Answer 21

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.

Question 22

Describe the process of notch signaling.

Answer 22

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.

Question 23

Delta-Notch signaling:
Different ways that it can work, what cells receive the signal?

Answer 23

only adjacent cells will receive the signal.

Question 24

Delta-Notch signaling:
Lateral Inhibition

Answer 24

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

Question 25

Delta-Notch signaling:
Induction

Answer 25

One cell induces another cell to change fate = often a binary fate decision.

Question 26

Before Notch signaling is activated, the __________________ acts as a transcriptional repressor.
What do you think is bound to this?

Answer 26

CSL transcription factor.
HDAC is bound to it!

Question 27

Mechanism of Notch activity:
When Delta binds to Notch, what do you think happens to the Notch receptor that allows the protease Presenilin to cleave the Notch in the transmembrane region?

Answer 27

There’s a conformation change that opens up a site for the protease to bind.