The role of SHIP in cytokine-induced signaling.
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-P3). This membrane-associated phospholipid, which is rapidly, albeit transiently, synthesized from PI-4,5-P2 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-P3 back to PI-4,5-P2 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-P3 to PI-3,4-P2. 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.
Kalesnikoff
J
J
The Terry Fox Laboratory, BC Cancer Agency, Vancouver, V5Z 1L3, Canada.
Sly
L M
LM
Hughes
M R
MR
Büchse
T
T
Rauh
M J
MJ
Cao
L-P
LP
Lam
V
V
Mui
A
A
Huber
M
M
Krystal
G
G
D000818:Animals; D016207:Cytokines / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D018909:src Homology Domains
D016207:Cytokines; D018129:Phosphatidylinositol Phosphates; C060974:phosphatidylinositol 3,4,5-triphosphate; D019869:Phosphatidylinositol 3-Kinases; D010744:Phosphoric Monoester Hydrolases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases