Reversible Ser/Thr SHIP phosphorylation: a new paradigm in phosphoinositide signalling?: Targeting of SHIP1/2 phosphatases may be controlled by phosphorylation on Ser and Thr residues.
Phosphoinositide (PI) phosphatases such as the SH2 domain-containing inositol 5-phosphatases 1/2 (SHIP1 and 2) are important signalling enzymes in human physiopathology. SHIP1/2 interact with a large number of immune and growth factor receptors. Tyrosine phosphorylation of SHIP1/2 has been considered to be the determining regulatory modification. However, here we present a hypothesis, based on recent key publications, highlighting the determining role of Ser/Thr phosphorylation in regulating several key properties of SHIP1/2. Since a subunit of the Ser/Thr phosphatase PP2A has been shown to interact with SHIP2, a putative mechanism for reversing SHIP2 Ser/Thr phosphorylation can be anticipated. PI phosphatases are potential target molecules in human diseases, particularly, but not exclusively, in cancer and diabetes. Therefore, this novel regulatory mechanism deserves further attention in the hunt for discovering novel or complementary therapeutic strategies. This mechanism may be more broadly involved in regulating PI signalling in the case of synaptojanin1 or the phosphatase, tensin homolog, deleted on chromosome TEN.
Institut de Recherche Interdisciplinaire (IRIBHM), Université Libre de Bruxelles, Campus Erasme, Brussels, Belgium.
William's Elong
WE
Edimo
Veerle
V
Janssens
Etienne
E
Waelkens
Christophe
C
Erneux
D000818:Animals; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D000072181:Inositol Polyphosphate 5-Phosphatases; D051379:Mice; D018345:Mice, Knockout; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D012694:Serine / Q000378:metabolism*; D015398:Signal Transduction; D013379:Substrate Specificity; D013912:Threonine / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D000099182:Phosphoinositide 5-Phosphatases
D000072181:Inositol Polyphosphate 5-Phosphatases; D051059:PTEN Phosphohydrolase; D018129:Phosphatidylinositol Phosphates; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases; D012694:Serine; D013912:Threonine; D014443:Tyrosine; D000099182:Phosphoinositide 5-Phosphatases; C060974:phosphatidylinositol 3,4,5-triphosphate; C494929:PTEN protein, human; C000606430:INPP5D protein, human; C098706:INPPL1 protein, human; C000606433:Inpp5d protein, mouse; C000606435:Inppl1 protein, mouse