Abnormal Chemokine-Induced Responses of Immature and Mature Hematopoietic Cells from Motheaten Mice Implicate the Protein Tyrosine Phosphatase Shp-1 in Chemokine Responses

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 (mev/mev) 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 mev/mev versus wild-type (+/+) mice. SDF-1–dependent actin polymerization and activation of mitogen-activated protein kinases were also greater in mev/mev versus +/+ cells. In contrast, immature subsets of mev/mev 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 mev/mev T cells. Our results implicate SHP-1 involvement in a number of different chemokine-induced biological activities.

• Publication year

  1999

• Venue

  Journal of Experimental Medicine

• Publication date

  1999-09-06

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1084/JEM.190.5.681PMID 10477552PMCID 2195618
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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