ABSTRACT
INTRODUCTION Many key processes of cellular activity are regulated by the opposing action of protein kinases and phosphatases, which phosphorylate and dephosphorylate proteins, respectively. The human genome encodes 518 different kinases (1,2) and 142 different protein phosphatases (3). The human “kinome” has been subdivided into seven groups (4) comprising (i) TK (tyrosine kinases, including receptor kinases), (ii) TKL (tyrosine kinase-like kinases), (iii) STE (homologues of yeast sterile 7, 11, and 20 kinases), (iv) CK1 (casein kinase 1), (v) AGC (containing the cyclic nucleotide-dependent protein kinase A & G families and the lipid-dependent protein kinase C family), (vi) CaMK (calcium/calmodulindependent protein kinase), and (vii) CMGC [containing the CDK (cyclindependent kinase), MAPK (mitogen-activated protein kinase), GSK3 (glycogen synthase kinase), and CLK (Cdc-2-like kinase) families]. Phosphatases have been similarly grouped by substrate specificity into ser/thr, tyr, and dual-specificity classes. Furthermore, the “conventional” Tyr phosphatases have been classified as those specific for phosphorylated Tyr residues (PTPs), whereas dualspecificity phosphatases (DSPs) act at phosphorylated Tyr and Ser/Thr residues (5). Similarly, the 107 PTPs have been divided into four families based on the amino acid sequences of their catalytic domains (6), each having a range of substrate specificities. Most of the PTPs are posttranslationally modified but glycosylation is apparently restricted to the transmembrane PTPs. Like kinases, the most common form of modification of PTPs is ser, thr, or tyr phosphorylation and this has been shown to regulate their catalytic activity. This key role played by PTPs in maintaining the level of tyr phosphorylation of various proteins in cells may be an important contributing factor in the physiological regulation of cellular activity.
