Related Experiment Videos
Low M(r) phosphotyrosine protein phosphatase interacts with the PDGF receptor directly via its catalytic site
P Chiarugi1, P Cirri, G Raugei
1Departimento di Scienze Biochimiche di Firenze, Università di Firenze, Italy.
Abstract:
Many proteins bind to the activated platelet derived growth factor receptor (PDGF-R) either directly or by means of adapter molecules. Up to now all these proteins were shown to transmit and amplify the signal started with PDGF-R stimulation. In a recent study our group had demonstrated that low M(r) phosphotyrosine protein phosphatase (LMW-PTP) specifically interacts with PDGF-R in NIH3T3 cells. In the present study we have attempted to clarify the modality of interaction, both in vivo and in vitro, of these two proteins, using a catalytically inactive LMW-PTP mutant. Our results indicate that LMW-PTP and PDGF-R interact directly, without the necessity of any adapter protein. This interaction leads to PDGF-R dephosphorylation and, presumably, interrupts one or more of the mitogenic pathways that originate from receptor activation.
Insights
Low molecular weight protein tyrosine phosphatase (LMW-PTP) directly binds and dephosphorylates platelet-derived growth factor receptor (PDGF-R), interrupting signaling pathways. This interaction does not require adapter proteins.
Area of Science:
- Cellular signaling
- Molecular biology
- Biochemistry
Background:
- Platelet-derived growth factor receptor (PDGF-R) activation initiates signaling cascades.
- Numerous proteins interact with PDGF-R, typically amplifying its signal.
- Previous work identified an interaction between low molecular weight phosphotyrosine protein phosphatase (LMW-PTP) and PDGF-R.
Purpose of the Study:
- To elucidate the interaction mechanism between LMW-PTP and PDGF-R.
- To determine if adapter proteins mediate the LMW-PTP and PDGF-R interaction.
- To investigate the functional consequence of LMW-PTP binding on PDGF-R signaling.
Main Methods:
- In vivo and in vitro interaction studies.
- Utilized a catalytically inactive mutant of LMW-PTP.
- NIH3T3 cells were used for experiments.
Main Results:
- LMW-PTP directly interacts with PDGF-R.
- The interaction occurs independently of any adapter proteins.
- LMW-PTP binding leads to PDGF-R dephosphorylation.
Conclusions:
- LMW-PTP directly binds to PDGF-R.
- This direct interaction dephosphorylates PDGF-R.
- The dephosphorylation likely interrupts PDGF-R-mediated mitogenic signaling pathways.