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

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

SUBMITTER: Stuible M 

PROVIDER: S-EPMC2911340 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature