Phosphorylation of proteins on tyrosine residues is regulated by the activities 
of protein tyrosine kinases and protein tyrosine phosphatases. Anaplastic 
lymphoma kinase (ALK) is a receptor tyrosine kinase (RTK) essentially and 
transiently expressed during development of the central and peripheral nervous 
systems. ALK has been identified as a major neuroblastoma predisposition gene 
and activating mutations have been identified in a subset of sporadic 
neuroblastoma tumors. We previously established that the mutated receptors were 
essentially retained in the endoplasmic reticulum/Golgi compartments due to 
their constitutive activity. Intriguingly we demonstrated a stronger 
phosphorylation for the minor pool of receptor addressed to the plasma membrane. 
We decided to investigate the potential involvement of tyrosine phosphatase in 
dephosphorylation of this intracellular pool. In this study we first showed that 
general inhibition of tyrosine phosphatases resulted in a dramatic increase of 
the tyrosine phosphorylation of the wild type but also of the mutated receptors. 
This increase not only required the intrinsic kinase activity of the ALK 
receptor but also involved the Src tyrosine kinase family. Second we provided 
strong evidences that the endoplasmic reticulum associated phosphatase PTP1B is 
key player in the control of ALK phosphorylation. Our data shed a new light on 
the biological significance of the basal phosphorylation levels of both wild 
type and mutated ALK receptors and could be essential to further understand 
their roles in malignancies.