Control of \\{ALK\\} (wild type and mutated forms) phosphorylation: Specific role of the phosphatase \\{PTP1B\\}

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作者：

M.C. Boutterin and P. Mazot and C. Faure and S. Doly and N. Gervasi and M.L. Tremblay and M. Vigny

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摘要：

Abstract 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.

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关键词：

ALK Mutated receptors Phosphorylation Phosphatase PTP1B

DOI：

10.1016/j.cellsig.2013.02.020

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年份：

2013