MOLECULAR-CLONING OF A PROTEIN SERINE THREONINE PHOSPHATASE CONTAINING A PUTATIVE REGULATORY TETRATRICOPEPTIDE REPEAT DOMAIN/

Two novel protein serine/threonine phosphatases were cloned from a rat fat cell library with probes generated by a polymerase chain reaction -based cloning approach. One of these cDNAs encoded a protein presumab ly representing the rat homologue of PPV from Drosophila (75% identity of amino acids). The other novel cDNA encoded a protein phosphatase o f 499 amino acids and was designated PPT. Its catalytic domain contain s motifs typical for protein phosphatases but is only distantly relate d with PP1, PP2A, and PP2B (38-42% identical amino acids). When expres sed in Escherichia coli, the catalytic domain of PPT exhibited protein phosphatase activity (dephosphorylation of phosphorylase a) that was inhibitable by okadaic acid. As a unique feature among other members o f this gene family, PPT has an amino terminal extension of 200 amino a cids harboring three tandemly arranged tetratricopeptide repeat (TPR) motifs. This domain has previously been found in other proteins involv ed in the regulation of RNA synthesis or mitosis. mRNA of PPT was pred ominantly found in brain and, in lower levels, in testis, but was near ly undetectable in spleen, lung, skeletal muscle, kidney, and liver. I t is suggested that the TPR domain of PPT may be involved in the regul ation of the function of this novel protein phosphatase.