ACTH Modulates PTP-PEST Activity and Promotes Its Interaction With Paxillin

J Cell Biochem. 2016 Sep;117(9):2170-81. doi: 10.1002/jcb.25566. Epub 2016 May 8.

Abstract

Adrenocorticotropic hormone (ACTH) treatment has been proven to promote paxillin dephosphorylation and increase soluble protein tyrosine phosphatase (PTP) activity in rat adrenal zona fasciculata (ZF). Also, in-gel PTP assays have shown the activation of a 115-kDa PTP (PTP115) by ACTH. In this context, the current work presents evidence that PTP115 is PTP-PEST, a PTP that recognizes paxillin as substrate. PTP115 was partially purified from rat adrenal ZF and PTP-PEST was detected through Western blot in bioactive samples taken in each purification step. Immunohistochemical and RT-PCR studies revealed PTP-PEST expression in rat ZF and Y1 adrenocortical cells. Moreover, a PTP-PEST siRNA decreased the expression of this phosphatase. PKA phosphorylation of purified PTP115 isolated from non-ACTH-treated rats increased KM and VM . Finally, in-gel PTP assays of immunoprecipitated paxillin from control and ACTH-treated rats suggested a hormone-mediated increase in paxillin-PTP115 interaction, while PTP-PEST and paxillin co-localize in Y1 cells. Taken together, these data demonstrate PTP-PEST expression in adrenal ZF and its regulation by ACTH/PKA and also suggest an ACTH-induced PTP-PEST-paxillin interaction. J. Cell. Biochem. 117: 2170-2181, 2016. © 2016 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.

Keywords: ACTH; ADRENAL ZONA FASCICULATA; PAXILLIN; PHOSPHORYLATION; PROTEIN TYROSINE PHOSPHATASE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenocorticotropic Hormone / pharmacology*
  • Animals
  • Cell Line, Tumor
  • Cyclic AMP-Dependent Protein Kinases / genetics
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Mice
  • Paxillin / genetics
  • Paxillin / metabolism*
  • Protein Binding / drug effects
  • Protein Tyrosine Phosphatase, Non-Receptor Type 12 / biosynthesis*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 12 / genetics
  • Rats
  • Zona Fasciculata / cytology
  • Zona Fasciculata / metabolism*

Substances

  • Paxillin
  • Pxn protein, rat
  • Adrenocorticotropic Hormone
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Tyrosine Phosphatase, Non-Receptor Type 12