SHP-1 regulates Fcγ receptor-mediated phagocytosis and the activation of RAC

Anita M. Kant, Pradip De, Xiaodong Peng, Taolin Yi, David J. Rawlings, Jong Suk Kim, Donald L Durden

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Fcγ receptor-mediated phagocytosis is a complex process involving the activation of protein tyrosine kinases, events that are potentially down-regulated by protein tyrosine phosphatases. We used the J774A.1 macrophage cell line to examine the roles played by the protein tyrosine phosphatase SHP-1 in the negative regulation of Fcγ receptor-mediated phagocytosis, Stimulation with sensitized sheep red blood cells (sRBCs) induced tyrosine phosphorylation of CBL and association of CBL with CRKL. These events were completely or partially abrogated by PP1 or the heterologous expression of dominant-negative SYK, respectively. Heterologous expression of wild-type but not catalytically inactive SHIP-1 also completely abrogated the phagocytosis of IgG-sensitized sRBCs. Most notably, overexpressed SHP-1 associates with CBL and this association led to CBL dephosphorylation, loss of the CBL-CRKL interaction, and the suppression of Rac activation. These data represent the first direct evidence that SHP-1 is involved in the regulation of Fcγ receptor-mediated phagocytosis and suggest that activating signals mediated by SRC family kinases SYK, CBL, phosphatidyl inositol-3 (PI-3) kinase, and Rac are directly opposed by inhibitory signals through SHP-1.

Original languageEnglish (US)
Pages (from-to)1852-1859
Number of pages8
JournalBlood
Volume100
Issue number5
StatePublished - Sep 1 2002

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Fc Receptors
Phagocytosis
Chemical activation
Blood
Phosphotransferases
Non-Receptor Type 6 Protein Tyrosine Phosphatase
Cells
Association reactions
Sheep
Phosphorylation
Protein Tyrosine Phosphatases
Macrophages
Erythrocytes
Phosphatidylinositols
Protein-Tyrosine Kinases
Tyrosine
Immunoglobulin G
Cell Line

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Kant, A. M., De, P., Peng, X., Yi, T., Rawlings, D. J., Kim, J. S., & Durden, D. L. (2002). SHP-1 regulates Fcγ receptor-mediated phagocytosis and the activation of RAC. Blood, 100(5), 1852-1859.

SHP-1 regulates Fcγ receptor-mediated phagocytosis and the activation of RAC. / Kant, Anita M.; De, Pradip; Peng, Xiaodong; Yi, Taolin; Rawlings, David J.; Kim, Jong Suk; Durden, Donald L.

In: Blood, Vol. 100, No. 5, 01.09.2002, p. 1852-1859.

Research output: Contribution to journalArticle

Kant, AM, De, P, Peng, X, Yi, T, Rawlings, DJ, Kim, JS & Durden, DL 2002, 'SHP-1 regulates Fcγ receptor-mediated phagocytosis and the activation of RAC', Blood, vol. 100, no. 5, pp. 1852-1859.
Kant AM, De P, Peng X, Yi T, Rawlings DJ, Kim JS et al. SHP-1 regulates Fcγ receptor-mediated phagocytosis and the activation of RAC. Blood. 2002 Sep 1;100(5):1852-1859.
Kant, Anita M. ; De, Pradip ; Peng, Xiaodong ; Yi, Taolin ; Rawlings, David J. ; Kim, Jong Suk ; Durden, Donald L. / SHP-1 regulates Fcγ receptor-mediated phagocytosis and the activation of RAC. In: Blood. 2002 ; Vol. 100, No. 5. pp. 1852-1859.
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