T-cell protein tyrosine phosphatase (Tcptp) is a negative regulator of colony-stimulating factor 1 signaling and macrophage differentiation

Paul D. Simoncic, Annie Bourdeau, Ailsa Lee-Loy, Larry R. Rohrschneider, Michel L. Tremblay, E. Richard Stanley, C. Jane McGlade

Research output: Contribution to journalArticle

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Abstract

Mice null for the T-cell protein tyrosine phosphatase (Tcptp-/-) die shortly after birth due to complications arising from the development of a systemic inflammatory disease. It was originally reported that Tcptp -/- mice have increased numbers of macrophages in the spleen; however, the mechanism underlying the aberrant growth and differentiation of macrophages in Tcptp-/- mice is not known. We have identified Tcptp as an important regulator of colony-stimulating factor 1 (CSF-1) signaling and mononuclear phagocyte development. The number of CSF-1-dependent CFU is increased in Tcptp-/- bone marrow. Tcptp-/- mice also have increased numbers of granulocyte-macrophage precursors (GMP), and these Tcptp-/- GMP yield more macrophage colonies in response to CSF-1 relative to wild-type cells. Furthermore, we have identified the CSF-1 receptor (CSF-1R) as a physiological target of Tcptp through substrate-trapping experiments and its hyperphosphorylation in Tcptp-/- macrophages. Tcptp-/- macrophages also have increased tyrosine phosphorylation and recruitment of a Grb2/Gab2/Shp2 complex to the CSF-1R and enhanced activation of Erk after CSF-1 stimulation, which are important molecular events in CSF-1-induced differentiation. These data implicate Tcptp as a critical regulator of CSF-1 signaling and mononuclear phagocyte development in hematopoiesis.

Original languageEnglish (US)
Pages (from-to)4149-4160
Number of pages12
JournalMolecular and Cellular Biology
Volume26
Issue number11
DOIs
StatePublished - Jun 2006

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Non-Receptor Type 2 Protein Tyrosine Phosphatase
Macrophage Colony-Stimulating Factor
Macrophages
Phagocytes
Granulocytes
Colony-Stimulating Factor Receptors
Macrophage Colony-Stimulating Factor Receptors
Null Lymphocytes
Hematopoiesis

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Simoncic, P. D., Bourdeau, A., Lee-Loy, A., Rohrschneider, L. R., Tremblay, M. L., Stanley, E. R., & McGlade, C. J. (2006). T-cell protein tyrosine phosphatase (Tcptp) is a negative regulator of colony-stimulating factor 1 signaling and macrophage differentiation. Molecular and Cellular Biology, 26(11), 4149-4160. https://doi.org/10.1128/MCB.01932-05

T-cell protein tyrosine phosphatase (Tcptp) is a negative regulator of colony-stimulating factor 1 signaling and macrophage differentiation. / Simoncic, Paul D.; Bourdeau, Annie; Lee-Loy, Ailsa; Rohrschneider, Larry R.; Tremblay, Michel L.; Stanley, E. Richard; McGlade, C. Jane.

In: Molecular and Cellular Biology, Vol. 26, No. 11, 06.2006, p. 4149-4160.

Research output: Contribution to journalArticle

Simoncic, PD, Bourdeau, A, Lee-Loy, A, Rohrschneider, LR, Tremblay, ML, Stanley, ER & McGlade, CJ 2006, 'T-cell protein tyrosine phosphatase (Tcptp) is a negative regulator of colony-stimulating factor 1 signaling and macrophage differentiation', Molecular and Cellular Biology, vol. 26, no. 11, pp. 4149-4160. https://doi.org/10.1128/MCB.01932-05
Simoncic, Paul D. ; Bourdeau, Annie ; Lee-Loy, Ailsa ; Rohrschneider, Larry R. ; Tremblay, Michel L. ; Stanley, E. Richard ; McGlade, C. Jane. / T-cell protein tyrosine phosphatase (Tcptp) is a negative regulator of colony-stimulating factor 1 signaling and macrophage differentiation. In: Molecular and Cellular Biology. 2006 ; Vol. 26, No. 11. pp. 4149-4160.
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