Altered responsiveness to chemokines due to targeted disruption of SHIP

Chang H. Kim, Giao Hangoc, Scott Cooper, Cheryl D. Helgason, Sandie Yew, R. Keith Humphries, Gerald Krystal, Hal E. Broxmeyer

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Abstract

SHIP has been implicated in negative signaling in a number of hematopoietic cell types and is postulated to downregulate phosphatidylinositol-3-kinase- (PI-3K-) initiated events in diverse receptor signaling pathways. Because PI-3K is implicated in chemokine signaling, we investigated whether SHIP plays any role in cellular responses to chemokines. We found that a number of immature and mature hematopoietic cells from SHIP- deficient mice manifested enhanced directional migration (chemotaxis) in response to the chemokines stromal cell-derived factor-1 (SDF-1) and B- lymphocyte chemoattractant (BLC). SHIP(-/-) cells were also more active in calcium influx and actin polymerization in response to SDF-1. However, colony formation by SHIP-deficient hematopoietic progenitor cell (HPCs) was not inhibited by 13 myelosuppressive chemokines that normally inhibit proliferation of HPCs. These altered biologic activities of chemokines on SHIP-deficient cells are not caused by simple modulation of chemokine receptor expression in SHIP-deficient mice, implicating SHIP in the modulation of chemokine-induced signaling and downstream effects.

Original languageEnglish (US)
Pages (from-to)1751-1759
Number of pages9
JournalJournal of Clinical Investigation
Volume104
Issue number12
DOIs
StatePublished - Dec 1999

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kim, C. H., Hangoc, G., Cooper, S., Helgason, C. D., Yew, S., Humphries, R. K., Krystal, G., & Broxmeyer, H. E. (1999). Altered responsiveness to chemokines due to targeted disruption of SHIP. Journal of Clinical Investigation, 104(12), 1751-1759. https://doi.org/10.1172/JCI7310