STEP: a family of brain-enriched PTPs. Alternative splicing produces transmembrane, cytosolic and truncated isoforms.
The family of striatal enriched phosphatases (STEPs) consists of protein tyrosine phosphatases (PTPs) that are enriched within the central nervous system. Previous biochemical studies have shown that the STEP family includes transmembrane, as well as soluble, cytosolic proteins. We now extend these findings with the isolation and characterization of a new, truncated member of this family, termed STEP38. The cDNA of STEP38 encodes a protein of 346 amino acids with a predicted mobility of 38 kDa. In contrast to the cytosolic variants, it contains two hydrophobic amino acid sequences at its N-terminus, two sequences enriched in Pro, Glu, Asp, Ser and Thr residues (PEST sequences), and two polyproline domains. We have used differential centrifugation, continuous sucrose gradients, and transfection experiments to clarify the subcellular localization of STEP38 within membrane compartments. These experiments suggest that a pool of STEP38 is targeted to membrane compartments of the endoplasmic reticulum. The STEP38 cDNA contains a stop codon upstream of the catalytic phosphatase domain that is normally present in other STEP variants, and enzymatic assays conform that STEP38 is inactive. Thus, the STEP family consists of cytosolic, transmembrane, and truncated isoforms. These findings are similar to what has been found for some members of the protein tyrosine kinase (PTK) family that uses alternative splicing mechanisms to produce active and inactive variants. By analogy with suggested mechanisms of action for the truncated PTKs, inactive STEP isoforms may participate in signaling events by protecting potential substrates from dephosphorylation by other members of this family.
Bult
A
A
Child Study Center, Yale University School of Medicine, New Haven, CT 06520-7900, USA.
Zhao
F
F
Dirkx
R
R
Raghunathan
A
A
Solimena
M
M
Lombroso
P J
PJ
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D016466:CHO Cells / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000737:chemistry; D037281:Calnexin; D006224:Cricetinae; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D008565:Membrane Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D051381:Rats; D016708:Synaptophysin / Q000737:chemistry; D014162:Transfection
D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; D016708:Synaptophysin; D037281:Calnexin; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C489931:Ptpn5 protein, rat