Analysis of functional and structural domains of a mitogen-induced protein tyrosine phosphatase

Abstract

Phosphorylation of proteins on tyrosyl residues is a key mechanism by which multiple newlinecellular events are regulated. The stimuli, as diverse as those that dictate whether a cell newlinewould grow, divide, change shape, move, differentiate or die, transmit signals via pathways newlineinvolving tyrosyl phosphorylation of specific cellular proteins. At steady state, the newlinephosphorylation of a tyrosyl residue depends on the relative activities of protein tyrosine newlinekinases (PTKs) and protein tyrosine phosphatases (PTPs). Since tyrosine phosphorylation of newlineproteins in vivo is a transient and reversible event, it is particularly important that the newlineactivities of these enzymes are stringently regulated. newlineUntil recently, little was known about PTPs. Since the discovery of PTK activity, newlinethere was a rapid progress in understanding the structure, function and regulation of PTKs. newlineSimilar progress was not possible with PTPs smce the pure preparations of PTP and newlinecorresponding sequence was not available until 1988. This was also compounded by the newlinebelief that the PTPs were few in number and subserve house keeping functions. However, newlinethe sequencing of human placental PTP, PTPlB and subsequent discovery that leucocyte cell newlinesurface molecule, CD45 is a receptor type PTP, lead to the discovery of a large diverse family newlineof PTPs in eukaryotes from yeast to man, as well as in some bacterial species. PTPs are newlinegrouped into two structural classes, receptor and non-receptor types. The receptor type possess newlinean extracellular domain for ligand binding and one or two intracellular phosphatase domains. newlineThe non-receptor type PTPs possess a single phosphatase (catalytic) domain and non-catalytic newlinedomains. The phosphatase domain is highly conserved within and across the species, while newlinethe non-catalytic domains are diverse and unique to individual phosphatases. The tyrosine newlinephosphatase catalytic domain does not show any homology to serine/threonine specific protein newlinephosphatases.