In control at the ER: PTP1B and the down-regulation of RTKs by dephosphorylation and endocytosis.
Receptor tyrosine kinases (RTKs) control the cellular response to a range of stimuli by binding extracellular factors and transmitting appropriate signals to intracellular sites. Protein tyrosine phosphatase 1B (PTP1B) modulates the activity of several RTKs by directly targeting the phosphorylated tyrosine residues that dictate their signaling output. Interestingly, the phenotypes of PTP1B deficiency in different contexts point to a more complex role in regulating RTK signaling. Exciting recent results indicate that the endocytic down-regulation of RTKs could be directly controlled by PTP1B. Microscopy studies have demonstrated an effect of PTP1B on post-endocytic internalization of RTKs into multivesicular bodies, and specific substrates that could influence their endosomal trafficking have been identified. These findings reveal a novel link between two important mechanisms of RTK signal attenuation and highlight the multifaceted impact of PTP1B on cell signaling.
Stuible
Matthew
M
Rosalind and Morris Goodman Cancer Centre and Departments of Biochemistry and Oncology, McGill University, Montreal, Quebec, Canada.
Tremblay
Michel L
ML
D000818:Animals; D015536:Down-Regulation; D004705:Endocytosis; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction
D020794:Receptor Protein-Tyrosine Kinases; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1