| First Author | Kim CH | Year | 1999 |
| Journal | J Clin Invest | Volume | 104 |
| Issue | 12 | Pages | 1751-9 |
| PubMed ID | 10606629 | Mgi Jnum | J:110864 |
| Mgi Id | MGI:3641406 | Doi | 10.1172/JCI7310 |
| Citation | Kim CH, et al. (1999) Altered responsiveness to chemokines due to targeted disruption of SHIP. J Clin Invest 104(12):1751-9 |
| abstractText | 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. |
