Abstract
Protein-tyrosine phosphatase 1B (PTP1B) is a ubiquitously expressed PTP that is anchored to the endoplasmic reticulum (ER). PTP1B dephosphorylates activated receptor tyrosine kinases after endocytosis, as they transit past the ER. However, PTP1B also can access some plasma membrane (PM)-bound substrates at points of cell-cell contact. To explore how PTP1B interacts with such substrates, we utilized quantitative cellular imaging approaches and mathematical modeling of protein mobility. We find that the ER network comes in close proximity to the PM at apparently specialized regions of cell-cell contact, enabling PTP1B to engage substrate(s) at these sites. Studies using PTP1B mutants show that the ER anchor plays an important role in restricting its interactions with PM substrates mainly to regions of cell-cell contact. In addition, treatment with PTP1B inhibitor leads to increased tyrosine phosphorylation of EphA2, a PTP1B substrate, specifically at regions of cell-cell contact. Collectively, our results identify PM-proximal sub-regions of the ER as important sites of cellular signaling regulation by PTP1B.
| Original language | English (US) |
|---|---|
| Article number | e36633 |
| Journal | PLoS One |
| Volume | 7 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 24 2012 |
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ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
Regulation of signaling at regions of cell-cell contact by endoplasmic reticulum-bound protein-tyrosine phosphatase 1B. / Haj, Fawaz; Sabet, Ola; Kinkhabwala, Ali; Wimmer-Kleikamp, Sabine; Roukos, Vassilis; Han, Hong Mei; Grabenbauer, Markus; Bierbaum, Martin; Antony, Claude; Neel, Benjamin G.; Bastiaens, Philippe I.
In: PLoS One, Vol. 7, No. 5, e36633, 24.05.2012.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Regulation of signaling at regions of cell-cell contact by endoplasmic reticulum-bound protein-tyrosine phosphatase 1B
AU - Haj, Fawaz
AU - Sabet, Ola
AU - Kinkhabwala, Ali
AU - Wimmer-Kleikamp, Sabine
AU - Roukos, Vassilis
AU - Han, Hong Mei
AU - Grabenbauer, Markus
AU - Bierbaum, Martin
AU - Antony, Claude
AU - Neel, Benjamin G.
AU - Bastiaens, Philippe I.
PY - 2012/5/24
Y1 - 2012/5/24
N2 - Protein-tyrosine phosphatase 1B (PTP1B) is a ubiquitously expressed PTP that is anchored to the endoplasmic reticulum (ER). PTP1B dephosphorylates activated receptor tyrosine kinases after endocytosis, as they transit past the ER. However, PTP1B also can access some plasma membrane (PM)-bound substrates at points of cell-cell contact. To explore how PTP1B interacts with such substrates, we utilized quantitative cellular imaging approaches and mathematical modeling of protein mobility. We find that the ER network comes in close proximity to the PM at apparently specialized regions of cell-cell contact, enabling PTP1B to engage substrate(s) at these sites. Studies using PTP1B mutants show that the ER anchor plays an important role in restricting its interactions with PM substrates mainly to regions of cell-cell contact. In addition, treatment with PTP1B inhibitor leads to increased tyrosine phosphorylation of EphA2, a PTP1B substrate, specifically at regions of cell-cell contact. Collectively, our results identify PM-proximal sub-regions of the ER as important sites of cellular signaling regulation by PTP1B.
AB - Protein-tyrosine phosphatase 1B (PTP1B) is a ubiquitously expressed PTP that is anchored to the endoplasmic reticulum (ER). PTP1B dephosphorylates activated receptor tyrosine kinases after endocytosis, as they transit past the ER. However, PTP1B also can access some plasma membrane (PM)-bound substrates at points of cell-cell contact. To explore how PTP1B interacts with such substrates, we utilized quantitative cellular imaging approaches and mathematical modeling of protein mobility. We find that the ER network comes in close proximity to the PM at apparently specialized regions of cell-cell contact, enabling PTP1B to engage substrate(s) at these sites. Studies using PTP1B mutants show that the ER anchor plays an important role in restricting its interactions with PM substrates mainly to regions of cell-cell contact. In addition, treatment with PTP1B inhibitor leads to increased tyrosine phosphorylation of EphA2, a PTP1B substrate, specifically at regions of cell-cell contact. Collectively, our results identify PM-proximal sub-regions of the ER as important sites of cellular signaling regulation by PTP1B.
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UR - http://www.scopus.com/inward/citedby.url?scp=84861379664&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0036633
DO - 10.1371/journal.pone.0036633
M3 - Article
C2 - 22655028
AN - SCOPUS:84861379664
VL - 7
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 5
M1 - e36633
ER -