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Altered PTPN13-β-catenin interaction by pathogenic mutations and involvement of this axis in B-cell receptor

David A Cabrera-Riofrío1,2, Hongbing Li3, Clara García-Calvo1,2

  • 1Departamento de Bioquímica y Biología Molecular, Universidad de Salamanca, Plaza Doctores de la Reina, s/n, Salamanca, 37007, Spain.

Scientific Reports
|December 20, 2025
PubMed

Insights

Protein tyrosine phosphatase non-receptor type 13 (PTPN13) mutations disrupt its interaction with β-catenin, impacting B-cell receptor signaling. This disruption contributes to lymphoid cell abnormalities and potential hematological disorders.

Area of Science:

  • Molecular Biology
  • Hematology
  • Cellular Signaling

Background:

  • Protein tyrosine phosphatase non-receptor type 13 (PTPN13) has dual roles in cancer.
  • PTPN13 interacts with β-catenin, a key regulator of the hematopoietic system.
  • PTPN13 mutations are linked to acute lymphoblastic leukemia (ALL), anemia, and inherited bone marrow failure (IBMF).

Purpose of the Study:

  • To investigate the functional consequences of PTPN13 mutations on the PTPN13-β-catenin interaction.
  • To elucidate the role of PTPN13 in B-cell receptor (BCR) signaling and lymphoid cell homeostasis.
  • To establish the PTPN13-β-catenin axis as a potential driver of hematological abnormalities.

Main Methods:

  • Analysis of PTPN13 mutations in patient families.
  • Assessment of PTPN13-β-catenin interaction.
  • Investigation of BCR signaling components (e.g., BTK activation) upon PTPN13 modulation.
  • Flow cytometry analysis of lymphoid cell surface markers (CD25, CD38).

Main Results:

  • Identified PTPN13 mutations impair the PTPN13-β-catenin interaction.
  • PTPN13 stabilizes β-catenin upon BCR activation.
  • PTPN13 silencing reduces Bruton's tyrosine kinase (BTK) activation and β-catenin levels.
  • Silencing PTPN13 or β-catenin alters CD25 and CD38 expression on lymphoid cells.

Conclusions:

  • The PTPN13-β-catenin axis is crucial for lymphoid cell homeostasis.
  • Disruption of this axis due to PTPN13 mutations can drive hematological abnormalities.
  • PTPN13 plays a significant role in modulating BCR signaling pathways.
Keywords:
Acute lymphoblastic leukaemia (ALL)B-cell receptor (BCR)Bruton tyrosine kinase (BTK)Inherited bone marrow failure (IBMF)PTPN13β-catenin

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