Abnormal chemokine-induced responses of immature and mature hematopoietic cells from motheaten mice implicate the protein tyrosine phosphatase SHP-1 in chemokine responses

Chang H. Kim, Cheng Kui Qu, Giao Hangoc, Scott Cooper, Nauyuki Anzai, Gen Sheng Feng, Hal E. Broxmeyer

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

Chemokines regulate a number of biological processes, including trafficking of diverse leukocytes and proliferation of myeloid progenitor cells. SHP-1 (Src homology 2 domain tyrosine phosphatase 1), a phosphotyrosine phosphatase, is considered an important regulator of signaling for a number of cytokine receptors. Since specific tyrosine phosphorylation of proteins is important for biological activities induced by chemokines, we examined the role of SHP-1 in functions of chemokines using viable motheaten (me(v)/me(v)) mice that were deficient in SHP-1. Chemotactic responses to stromal call-derived factor 1 (SDF-1), a CXC chemokine, were enhanced with bone marrow myeloid progenitor cells as well as macrophages, T cells, and B cells from me(v)/me(v) versus wild-type (+/+) mice. SDF-1- dependent actin polymerization and activation of mitogen-activated protein kinases were also greater in me(v)/me(v) versus +/+ cells. In contrast, immature subsets of me(v)/me(v) bone marrow myeloid progenitors were resistant to effects of a number of chemokines that suppressed proliferation of +/+ progenitors. These altered chemokine responses did not appear to be due to enhanced expression-of CXCR4 or lack of chemokine receptor expression. However, expression of some chemokine receptors (CCR1, CCR2, CCR3, and CXCR2) was significantly enhanced in me(v)/me(v) T cells. Our results implicate SHP- 1 involvement in a number of different chemokine-induced biological activites.

Original languageEnglish (US)
Pages (from-to)681-690
Number of pages10
JournalJournal of Experimental Medicine
Volume190
Issue number5
DOIs
StatePublished - Sep 6 1999

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Keywords

  • Chemokine
  • Chemotaxis
  • Myelosuppression
  • Src homology 2 domain tyrosine phosphatase 1
  • Stromal cell-derived factor 1
  • Viable motheaten mice

ASJC Scopus subject areas

  • Immunology

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