Lecture 25/26- March 6th- Cell Signaling and Stem Cells I/II
TODAY:
- Stem Cells
- Cellular signaling
Learning Outcomes:
- Analyze cell signaling pathways and predict the effects of protein changes
- Differentiate between kinases and phosphatases and understand their roles in cell signaling
cascades
- Predict whether a stem cell will undergo quiescence, self-renewal, or differentiate into a specific
cell type
Breakdown of Cell Signaling
Stage 1:
- A cell receives an external signal in the form of a molecule. (reception)
o The signaling molecule binds to a receptor on the cell surface
o External signaling molecule (protein, steroid hormone, etc) diffuses to the cell and binds
to its receptor protein, usually a transmembrane protein in the cell membrane
Stage 2:
- Signal transduction
o A series of chemical changes within the cell is triggered by receptor binding
o The physical form of the signal changes (ex. A signaling molecule binding to a receptor is
converted into a series of protein chemical transformations by adding or losing a
chemical species)
o The changes in receptor protein structure upon binding to the signaling molecule lead to
activation of the signal transduction pathway
o In theory, receptor changes the chemical properties of relay molecule #1 which then acts
upon relay molecule #2 and changes its properties, followed by the action of modified
relay molecule 2 on relay molecule 3 to change its properties.
Stage 3:
- Cellular response
o Cell changes the activity to specify for what is needed
o Often changes in the level of expression of specific genes within the nucleus
Signal Transduction
- Often a series of protein chemical transformation
- Two in particular being explored:
o Addition of a phosphate group carried out by a kinase protein
Kinases are usually very specific in the proteins that they target
Remove the phosphate group from a molecule of ATP and transfer it to a target
protein
Addition of a phosphate group will usually result in change of 3D structure of the
protein that is being modified
Tertiary or quaternary structure change
o Removal of a phosphate from a protein carried out by a phosphatase protein
, Phosphatases are usually very specific in the proteins that they target.
When the phosphate group is removed from a signaling molecule, that molecule
is turned off.
Phosphate is released into the cell and is recycled by reattaching it to ADP to
create ATP.
Signal Transduction and Stem Cell self-renewal
- R= receptor
- TK1= Kinase 1
- TK2=Kinase 2
- TF= transcription factor
- RNAP= RNA polymerase
These cells are in a quiescent state: cells is not
dividing nor differentiating. To do either requires
that a signal be received by the stem cell
SR= self renewal ligand
PO4= Phosphate added to protein
The binding of the self renewal ligand to the receptor
triggers a cascade of protein changes that leads to the
movement of the phosphorylated transcription factor
into the cell nucleus and activation of a set of genes
involved in triggering cell division and self-renewal
of the stem cell.