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LIF, HGF and G alpha s

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LIF, HGF and G alpha s

Postby kocho » Fri Dec 01, 2006 8:17 am

I am trying to figure out the signal cascade of this:

This group of embryonic stem cells have a temperature sensitive mutation in a Gas which is locked on at 33C and off at 37C. At 37C, these cells remain undifferentiated (self-renewal) in the presence of a cytokine (LIF) but differentiate into epithelial cells forming tubular structures in the presence of HGF (growth factor). When the cells are exposed to both LIF and HGF at 37C, the cells undergo self-renewal only. Repeating the above experiments at 33C resulted in the cells differentiating in all cases.

So far I have this:
When Gas is off; LIF through the JAK/STAT pathway causes self-renewal
HGF through MAPK causes differentiation
Now i dont know how LIF + HGF causes self-renewal; I don't know how the LIF pathway predominates.

When Gas is on; this cause adenylate cyclase to be active and causes the production of cAMP
I know that cAMP activates PKA which inhibits MAPK, so I dont know how you still get differentiation when Gas is on. Also I don't know how cAMP interacts with LIF, causing the LIF pathway to produce differentiated cells.
And how LIF + HGF causes differentiation.

Any help would be greatly appreciated!

THANK YOU!
kocho
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