PTP1B targets the endosomal sorting machinery: dephosphorylation of regulatory sites on the endosomal sorting complex required for transport component STAM2

Matthew Stuible; Jasmine V Abella; Matthew Feldhammer; Misha Nossov; Veena Sangwan; Blagoy Blagoev; Morag Park; Michel L Tremblay

doi:10.1074/jbc.M110.115295

PTP1B targets the endosomal sorting machinery

Authors:

Stuible, Matthew ;
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Abella, Jasmine V ;
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Feldhammer, Matthew ;
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Nossov, Misha ;
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Sangwan, Veena ;
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Blagoev, Blagoy ;
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0000-0002-3596-0066
Department of Biochemistry and Molecular Biology, Faculty of Science, University of Southern Denmark
Park, Morag ;
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Tremblay, Michel L
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Subtitle:

dephosphorylation of regulatory sites on the endosomal sorting complex required for transport component STAM2

DOI:

10.1074/jbc.M110.115295

Abstract:

Dephosphorylation and endocytic down-regulation are distinct processes that together control the signaling output of a variety of receptor tyrosine kinases (RTKs). PTP1B can directly dephosphorylate several RTKs, but it can also promote activation of downstream pathways through largely unknown mechanisms. These positive signaling functions likely contribute to the tumor-promoting effect of PTP1B in mouse cancer models. Here, we have identified STAM2, an endosomal protein involved in sorting activated RTKs for lysosomal degradation, as a substrate of PTP1B. PTP1B interacts with STAM2 at defined phosphotyrosine sites, and knockdown of PTP1B expression augments STAM2 phosphorylation. Intriguingly, manipulating the expression and phosphorylation state of STAM2 did not have a general effect on epidermal growth factor (EGF)-induced EGF receptor trafficking, degradation, or signaling. Instead, phosphorylated STAM2 specifically suppressed Akt activation, and a phosphorylation-deficient STAM2 mutant displayed prolonged localization on endosomes following EGF stimulation. These results reveal a novel link between the dephosphorylation and endocytic machinery and suggest that PTP1B can affect RTK signaling in a previously unrecognized manner.

Type:

Journal article

Language:

English

Published in:

Journal of Biological Chemistry, 2010, Vol 285, Issue 31, p. 23899-907

Main Research Area:

Science/technology

Publication Status:

Published

Review type:

Peer Review

Submission year:

2010

Scientific Level:

Scientific

ID:

78304278

PTP1B targets the endosomal sorting machinery

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