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Updated: May 10, 2026

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
Published on: July 17, 2020
A secreted PTEN phosphatase that enters cells to alter signaling and survival
Benjamin D Hopkins1, Barry Fine, Nicole Steinbach
1Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY 10029, USA.
Abstract:
Phosphatase and tensin homolog on chromosome ten (PTEN) is a tumor suppressor and an antagonist of the phosphoinositide-3 kinase (PI3K) pathway. We identified a 576-amino acid translational variant of PTEN, termed PTEN-Long, that arises from an alternative translation start site 519 base pairs upstream of the ATG initiation sequence, adding 173 N-terminal amino acids to the normal PTEN open reading frame. PTEN-Long is a membrane-permeable lipid phosphatase that is secreted from cells and can enter other cells. As an exogenous agent, PTEN-Long antagonized PI3K signaling and induced tumor cell death in vitro and in vivo. By providing a means to restore a functional tumor-suppressor protein to tumor cells, PTEN-Long may have therapeutic uses.
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