HOW do fetal stem cells begin their transformation into the specialised cells
that form our tissues and organs? That鈥檚 a question being asked by Tony Pawson,
a cell biologist at the Samuel Lunenfeld Research Institute of Mount Sinai
Hospital in Toronto.
Pawson and his team focus on the messaging systems within cells, specifically
the proteins called receptor tyrosine kinases (RTKs) that straddle the cell
membrane. RTKs are essentially gateways for information that allow cells to pick
up signals from outside and turn them into instructions that tell the cell to do
something different.
鈥淭he receptor crosses the outer membrane of the cell and acts as an antenna,鈥�
says Pawson. 鈥淥n the outside, it binds very strongly to a signalling molecule,
such as insulin,鈥� he says. 鈥淥n the inside, it has portions to communicate with
other proteins inside the cell.鈥� Activated RTKs might send a protein messenger
to the nucleus to activate new genes, for example, or trigger cell enzymes into
action.
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The big breakthrough came just over a decade ago when Pawson discovered a
link in the signalling chain called the SH2 domain. Domains are subregions of
larger proteins that have evolved within a variety of proteins. Pawson and
others have found that dozens of proteins鈥攆rom enzymes to transcription
factors鈥攈ave an SH2 domain, which enables all of them to relay information
from activated RTKs.
SH2 was just the start. Over the past decade, researchers have discovered
dozens more domains, each one with its own specialised function in the cell鈥檚
circuitry. Pawson鈥檚 latest work involves a signal that kick-starts the
transition of fetal stem cells into specialised cells during early development.
When a stem cell differentiates, it produces two unequal daughters. One is still
a stem cell, but the other has begun to differentiate into a specialised type of
cell, such as a blood stem cell.
The team traced the signal to a protein domain called PTB, which they traced
to a modular protein known to be active in one daughter cell but not the other.
The PTB domain also seems to relay signals from activated RTKs. Pawson says that
clues to how cells can be switched from one type to another could be vital in
the newly emerging field of therapeutic cloning, which holds the prospect of
growing organs for transplant from a patient鈥檚 own tissue.