Regulation of hematopoietic cell signaling by SHIP-1 inositol phosphatase: growth factors and beyond.

ABSTRACT

SHIP-1 is a hematopoietic-specific inositol phosphatase activated downstream of a multitude of receptors including those for growth factors, cytokines, antigen, immunoglobulin and toll-like receptor agonists where it exerts inhibitory control. While it is constitutively expressed in all immune cells, SHIP-1 expression is negatively regulated by the inflammatory and oncogenic micro-RNA miR-155. Knockout mouse studies have shown the importance of SHIP-1 in various immune cell subsets and have revealed a range of immune-mediated pathologies that are engendered due to loss of SHIP-1's regulatory activity, impelling investigations into the role of SHIP-1 in human disease. In this review, we provide an overview of the literature relating to the role of SHIP-1 in hematopoietic cell signaling and function, we summarize recent reports that highlight the dysregulation of the SHIP-1 pathway in cancers, autoimmune disorders and inflammatory diseases, and lastly we discuss the importance of SHIP-1 in restraining myeloid growth factor signaling.