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Identification of protein tyrosine phosphatases with specificity for the ligand-activated growth hormone receptor

Christian Pasquali1, Marie-Laure Curchod, Sébastien Wälchli

  • 1Serono Pharmaceutical Research Institute, 1228 Plan-les-Ouates, Geneva, Switzerland.

Molecular Endocrinology (Baltimore, Md.)
|August 9, 2003
PubMed

Insights

Seven protein tyrosine phosphatases (PTPs) were identified as specific for the phosphorylated human growth hormone receptor (GHR). Further analysis suggests PTP-H1 and PTP1B are key players in GHR signaling pathways.

Area of Science:

  • Biochemistry
  • Cellular Signaling
  • Molecular Biology

Background:

  • Protein tyrosine phosphatases (PTPs) are crucial regulators that deactivate tyrosine phosphorylation cascades initiated by cytokine receptors.
  • The human growth hormone receptor (GHR) intracellular domain is a key signaling component activated by phosphorylation.

Purpose of the Study:

  • To identify PTPs that specifically dephosphorylate the activated human GHR.
  • To investigate the role of specific PTPs in GHR signaling.

Main Methods:

  • Utilized substrate-trapping mutants of 31 PTPs to screen for specificity against phosphorylated GHR.
  • Employed Far Western blotting with physiologically phosphorylated GHR to validate PTP interactions.
  • Analyzed PTP substrate specificity for distinct GHR tyrosine residues.
  • Performed RT-PCR for mRNA tissue distribution and coexpression assays to assess dephosphorylation activity.

Main Results:

  • Seven PTPs (TC-PTP, PTP-beta, PTP1B, SAP-1, Pyst-2, Meg-2, PTP-H1) showed specificity for bacterial-expressed phosphorylated GHR.
  • TC-PTP, PTP1B, PTP-H1, and SAP-1 interacted with ligand-induced, physiologically phosphorylated GHR.
  • Identified distinct subsets of GHR tyrosines recognized by these PTPs.
  • PTP-H1 and PTP1B demonstrated potential involvement in GHR dephosphorylation.

Conclusions:

  • TC-PTP, PTP1B, PTP-H1, and SAP-1 are capable of recognizing the physiologically phosphorylated GHR.
  • PTP-H1 and PTP1B are identified as potential key regulators in GHR signaling due to their dephosphorylation activity and tissue distribution.

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