THE ROLE OF PHOSPHOTYROSINE PHOSPHATASES IN HEMATOPOIETIC-CELL SIGNAL-TRANSDUCTION

Phosphotyrosine phosphatases (PTPases) are the enzymes which remove ph osphate groups from protein tyrosine residues. An enormous number of p hosphatases have been cloned and sequenced during the past decade, man y of which are expressed in haematopoietic cells. This review focuses on the biochemistry and cell biology of three phosphatases, the transm embrane CD45 and the cytosolic SH2-domain-containing PTPases SHP-1 and SHP-2, to illustrate the diverse ways in which PTPases regulate recep tor signal transduction, The involvement of these and other PTPases ha s been demonstrated in haematopoietic cell development, apoptosis, act ivation and nonresponsiveness, A common theme in the actions of many h aematopoietic cell PTPases is the way in which they modulate the thres holds for receptor signalling, thereby regulating critical events in t he positive and negative selection of lymphocytes, There is growing in terest in haematopoietic PTPases and their associated regulatory prote ins as targets for pharmaceutical intervention and in the involvement of these enzymes in human disease.