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 Broxmeyer

Research output: Contribution to journalArticle

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

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Chemokines
Chemokine CXCL12
Hematopoietic Stem Cells
Phosphatidylinositol 3-Kinase
Chemokine Receptors
Chemotactic Factors
Chemotaxis
Phosphatidylinositol 3-Kinases
Polymerization
Actins
B-Lymphocytes
Down-Regulation
Cell Count
Calcium

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kim, C. H., Hangoc, G., Cooper, S., Helgason, C. D., Yew, S., Humphries, R. K., ... Broxmeyer, H. (1999). Altered responsiveness to chemokines due to targeted disruption of SHIP. Journal of Clinical Investigation, 104(12), 1751-1759.

Altered responsiveness to chemokines due to targeted disruption of SHIP. / Kim, Chang H.; Hangoc, Giao; Cooper, Scott; Helgason, Cheryl D.; Yew, Sandie; Humphries, R. Keith; Krystal, Gerald; Broxmeyer, Hal.

In: Journal of Clinical Investigation, Vol. 104, No. 12, 12.1999, p. 1751-1759.

Research output: Contribution to journalArticle

Kim, CH, Hangoc, G, Cooper, S, Helgason, CD, Yew, S, Humphries, RK, Krystal, G & Broxmeyer, H 1999, 'Altered responsiveness to chemokines due to targeted disruption of SHIP', Journal of Clinical Investigation, vol. 104, no. 12, pp. 1751-1759.
Kim CH, Hangoc G, Cooper S, Helgason CD, Yew S, Humphries RK et al. Altered responsiveness to chemokines due to targeted disruption of SHIP. Journal of Clinical Investigation. 1999 Dec;104(12):1751-1759.
Kim, Chang H. ; Hangoc, Giao ; Cooper, Scott ; Helgason, Cheryl D. ; Yew, Sandie ; Humphries, R. Keith ; Krystal, Gerald ; Broxmeyer, Hal. / Altered responsiveness to chemokines due to targeted disruption of SHIP. In: Journal of Clinical Investigation. 1999 ; Vol. 104, No. 12. pp. 1751-1759.
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