Activation of protein-tyrosine phosphatase SH-PTP2 by a tyrosine-based activation motif of a novel brain molecule.
BIT (a brain immunoglobulin-like molecule with tyrosine-based activation motifs) is a brain-specific membrane protein which has two cytoplasmic TAMs (tyrosine-based activation motifs). Using the Far Western blotting technique, we detected association of a 70-kDa protein with the tyrosine-phosphorylated TAMs of BIT. A mouse brain cDNA library in lambdagt11 was screened ... for this association, and two positive clones encoding tyrosine phosphatase SH-PTP2 were isolated. SH-PTP2 has two SH2 domains and is believed to function as a positive mediator in receptor tyrosine kinase signaling. SH-PTP2 and BIT were coimmunoprecipitated from phosphorylated rat brain lysate, and BIT was a major tyrosine-phosphorylated protein associated with SH-PTP2 in this lysate. This interaction was also observed in Jurkat T cells transfected with BIT cDNA depending on tyrosine phosphorylation of BIT. Bisphosphotyrosyl peptides corresponding to BIT-TAMs stimulated SH-PTP2 activity 33-35-fold in vitro, indicating that two SH2 domains of SH-PTP2 simultaneously interact with two phosphotyrosines of BIT-TAM. Our findings suggest that the tyrosine phosphorylation of BIT results in stimulation of the signal transduction pathway promoted by SH-PTP2 and that BIT is probably a major receptor molecule in the brain located just upstream of SH-PTP2.
Mesh Terms:
Amino Acid Sequence, Animals, Base Sequence, Blotting, Western, Brain, Cell Line, DNA Primers, Enzyme Activation, Humans, Intracellular Signaling Peptides and Proteins, Mice, Models, Structural, Molecular Sequence Data, Mutagenesis, Site-Directed, Nerve Tissue Proteins, Peptide Fragments, Phosphopeptides, Phosphorylation, Polymerase Chain Reaction, Protein Conformation, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, Rats, Receptors, Antigen, Recombinant Fusion Proteins, Signal Transduction, Transfection, Tyrosine
Amino Acid Sequence, Animals, Base Sequence, Blotting, Western, Brain, Cell Line, DNA Primers, Enzyme Activation, Humans, Intracellular Signaling Peptides and Proteins, Mice, Models, Structural, Molecular Sequence Data, Mutagenesis, Site-Directed, Nerve Tissue Proteins, Peptide Fragments, Phosphopeptides, Phosphorylation, Polymerase Chain Reaction, Protein Conformation, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, Rats, Receptors, Antigen, Recombinant Fusion Proteins, Signal Transduction, Transfection, Tyrosine
J. Biol. Chem.
Date: Oct. 11, 1996
PubMed ID: 8810330
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