- A new method of
imaging protein-protein interaction was developed by Dr. Stagljar and
colleagues called MYTH and MaMTH
- 300 interactions
between RTK and PTP were identified
between 58 RTKs and 144 PTPs were identified and a map will be created
research team led by Dr. Igor Stagljar
who was a professor in the University of Toronto's Donnelly Centre found
that there were two genes associated with triple-negative breast cancer, which
is difficult to treat.
Stagljar had a one-of-a kind way to find out how the proteins that were
produced by these two genes worked.
‘The receptor tyrosine kinases (RTK)- protein tyrosine phosphatase (PTP) protein interaction is essential for cancer prevention, MYTH and MaMTH technology is developed to study protein interactions.’
growth factor receptor (EGFR) was one of the proteins and it belonged to a
group called receptor tyrosine kinases (RTK).
These instruct the cell to
grow and multiply as a response to the signals
that are received from the cell's environment.
tyrosine phosphatase (PTP) is the other protein that was produced by the two
genes and the main way of working was by shutting down the receptor tyrosine
kinases. The epidermal growth factor is
present in the outer layer of the cell which makes it difficult to analyze
using traditional methods.
MYTH and MaMTH
MYTH and MaMTH technologies that were developed by Dr.Stagljar and his research
team which included Dr. Zhong Yao, one of the senior research associates in the
lab, were used to identify that the two proteins were in direct contact with
each other. It was then believed that certain forms of breast cancer were formed when the association
between these two proteins was disrupted. The disruption in the link was
found to result in uncontrolled signaling of RTK which lead to increased
proliferation of the cells.
Yao used the MYTH and MaMTH technologies to understand the various interactions
between all the RTK and the PTP present in humans. This aided in identifying
more than 300 interactions that were, thus far, unknown.
Dr. Stagljar said, "We tested interactions
between almost all 58 RTKs and 144 PTPs that exist in human cells. Our map
reveals new and surprising ways in which these proteins work together. These
insights will help us better understand what goes wrong in cancer in order to
develop more effective treatments." RTK in Cancers
advantage of the MYTH and MaMTH technology is in recording small interactions
between membrane proteins and in their natural setting which includes yeast as
well as mammalian cells
- RTKs are often hyperactive
and mutated in different types of cancers.
- Only a fifth
of RTKs have been detailed thus far and targeted by tyrosine kinase
believe that they are one of the best prospects as the tyrosine kinase
inhibitors specifically target forms of RTK that are mutated.
- The tyrosine
kinase inhibitors do not attack the normal version of the RTK.
- This method of
treatment would produce less side effects than traditional chemotherapy.
- The RTKs are present
inside the membrane of the cell, with some of their parts extending on
either side of the cell.
- The RTK gets
attached to phosphate group that is present on the tail of a signal
hormone, which is present below the surface and leads to the
development of biochemical reactions.
- This allows
the cells to grow and increase in number.
- The activation of
the RTKs is controlled by the PTPs.
- The PTPs remove
the additional phosphate group and stop the signaling cascade.
. The traditional methods
are unable to capture such fleeting interactions as the membranes need to be
removed, which moves the membrane protein apart.
of the interesting finds of the study
- The revelation
that some of the PTPs promote RTK signaling, indicative of a more complex
- PTPRA is a phosphatase that leads to the
activation of EGFR. EGFR is found
to be mutated in many types of cancers, highlighting a new method of
- There were two
new phosphatases that were identified,
PTPRB and PTPRH, that work by halting the EGFR signaling, showing
signs of anti-tumor response.
- MYTH and MaMTH
technology that was developed can be used to study RTK and PTP.
scientists hope to create a map with interactions between 3000 membrane
proteins. About 500 of these were found
to have a direct role in the development of many diseases among humans.
interaction between PTP and RTK is essential to understand the progress of
various diseases associated with humans. The MYTH and the MaMTH technology aided in understanding the short-lived interaction
between the two receptors and provided a clue to better drug targets.
- Regulation of Receptor Tyrosine Kinase Signaling by Protein Tyrosine Phosphatase-1B - (http://www.jbc.org/content/278/2/739.full)