The phosphatidylinositol (PI)-3 kinase (PI3K) pathway plays a central role in regulating many biological processes via the
generation of the key second messenger PI-3,4,5-trisphosphate (PI-3,4,5-P
3). This membrane-associated phospholipid, which is rapidly, albeit transiently, synthesized from PI-4,5-P
2 by PI3K in response to a diverse array of extracellular stimuli, attracts pleckstrin homology (PH) domain-containing proteins
to membranes to mediate its many effects. To ensure that the activation of this pathway is appropriately suppressed/terminated,
the ubiquitously expressed tumor suppressor PTEN hydrolyzes PI-3,4,5-P
3 back to PI-4,5-P
2 while the 145-kDa hemopoietic-restricted
SH2-containing
inositol 5′-
phosphatase, SHIP (also known as SHIP1), the 104-kDa
stem cell-restricted SHIP (sSHIP) and the more widely expressed 150-kDa SHIP2 hydrolyze PI-3,4,5-P
3 to PI-3,4-P
2. In this review we will concentrate on the properties of the three SHIPs, with special emphasis being placed on the role
that SHIP plays in cytokine-induced signaling.