CLONING AND EXPRESSION OF A CYTOSOLIC MEGAKARYOCYTE PROTEIN-TYROSINE-PHOSPHATASE WITH SEQUENCE HOMOLOGY TO RETINALDEHYDE-BINDING PROTEIN AND YEAST SEC14P

Protein tyrosine phosphorylation is important in the regulation of cel l growth, the cell cycle, and malignant transformation. We have cloned a cDNA that encodes a cytosolic protein-tyrosine-phosphatase (PTPase) , MEG2, from MEG-01 cell and human umbilical vein endothelial cell cDN A libraries. The 4-kilobase cDNA sequence of PTPase MEG2 corresponds i n length to the mRNA transcript detected by Northern blotting. The pre dicted open reading frame encodes a 68-kDa protein composed of 593 ami no acids and has no apparent signal or transmembrane sequences, sugges ting that it is a cytosolic protein. The C-terminal region has a PTPas e catalytic domain that has 30-40% amino acid identity to other known PTPases. The N-terminal region has 254 amino acids that are 28% identi cal to cellular retinaldehyde-binding protein and 24% identical to yea st SEC14p, a protein that has phosphatidylinositol transfer activity a nd is required for protein secretion through the Golgi complex in yeas t. Recombinant PTPase MEG2 expressed in Escherichia coli possesses PTP ase activity. PTPase MEG2 mRNA was detected in 12 cell lines tested, w hich suggests that this phosphatase is widely expressed. The structure of PTPase MEG2 implies that a tyrosine phosphatase could participate in the transfer of hydrophobic ligands or in functions of the Golgi ap paratus.