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Human protein tyrosine phosphatase‐σ: Alternative splicing and inhibition by bisphosphonates
Author(s) -
Endo Naoto,
Rutledge Su Jane,
Opas Evan E.,
Vogel Robert,
Rodan Gideon A.,
Schmidt Azriel
Publication year - 1996
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650110415
Subject(s) - alternative splicing , complementary dna , microbiology and biotechnology , protein tyrosine phosphatase , rna splicing , transmembrane protein , transmembrane domain , peptide sequence , fibronectin , biology , chemistry , amino acid , biochemistry , tyrosine , messenger rna , gene , rna , extracellular matrix , receptor
Two forms of the transmembrane human protein tyrosine phosphatase (PTPσ), generated by alternative splicing, were identified by cDNA cloning and Northern hybridization with selective cDNA probes. The larger form of PTPσ is expressed in various human tissues, human osteosarcoma, and rat tibia. The hPTPσ cDNA codes for a protein of 1911 amino acid residues and is composed of a cytoplasmic region with two PTP domains and an extracellular region that can be organized into three tandem repeats of immunoglobulin‐like domains and eight tandem repeats of fibronectin type III‐like domains. In the brain, the major transcript of PTPσ is an alternatively spliced mRNA, in which the coding region for the fibronectin type III‐like domains number four to seven are spliced out, thus coding for a protein of 1502 amino acid residues similar to the rat PTPσ and rat PTP‐NE3. Using in situ hybridization, we assigned hPTPσ to chromosome 6, arm 6q and band 6q15. The bacterial‐expressed hPTPσ exhibits PTPase activity that was inhibited by orthovanadate (IC 50 = 0.02 μM) and by two bisphosphonates used for the treatment of bone diseases, alendronate (ALN) (IC 50 = 0.5 μM) and etidronate (IC 50 = 0.2 μM). In quiescent calvaria osteoblasts, micromolar concentrations of vanadate, ALN and etidronate stimulate cellular proliferation. These findings show tissue‐specific alternative splicing of PTPσ and suggest that PTPs are putative targets of bisphosphonate action.