T-cell protein tyrosine phosphatase is a key regulator in immune cell signaling: lessons from the knockout mouse model and implications in human disease


Michel L. Tremblay
Rosalind and Morris Goodman Cancer Centre
1160 Pine Avenue West
Cancer Pavilion, room 602
Montreal, QC, Canada H3G 0B1
Tel.: +1 514 398 7290
Fax: +1 514 398 6769
e-mail: michel.tremblay@mcgill.ca


Summary:  The immune system requires for its proper ontogeny, differentiation, and maintenance the function of several tyrosine kinases and adapters that create and modify tyrosine phosphorylation sites. Tyrosine phosphorylation is a crucial protein modification in immune cell signaling and can be reversed by protein tyrosine phosphatases (PTPs). Much progress has been made in identifying and understanding PTP function in the immune system. In this review, we present one of these proteins, named T-cell PTPs (TC-PTP) (gene name PTPN2), a classical, non-receptor PTP that is ubiquitously expressed with particularly high expression in hematopoietic tissues. TC-PTP is remarkable not only by the fact that it appears to influence most, if not all, cells involved in the development of the immune system, from stem cells to differentiated lineages, but also recent findings have positioned it at the core of several human diseases from autoimmune disease to cancer.