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.Editor's suggested further reading in BioEssays: Pairing phosphoinositides with calcium ions in endolysosomal dynamics Abstract. (shrink)

The number of cellular events identified as being directly or indirectly modulated by phosphoinositides dramatically increased in the recent years. Part of the complexity results from the fact that the seven phosphoinositides play second messenger functions in many different areas of growth factors and insulin signaling, cytoskeletal organization, membrane dynamics, trafficking, or nuclear signaling. PtdIns(3,4)P2 is commonly reported as a product of the SH2 domain‐containing inositol 5‐phosphatases 1/2 (SHIP1 and SHIP2) that dephosphorylate PtdIns(3,4,5)P3 at the 5‐position. Here we discuss recent (...) interest in PtdIns(3,4)P2 signaling highlighting its involvement in key cellular mechanisms such as cell adhesion, migration, and cytoskeletal regulation. We question and discuss the involvement of SHIP2 either as a PI 5‐phosphatase or as a scaffold protein in insulin signaling, cytoskeletal dynamics, and endocytosis of growth factor receptors. (shrink)

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.Editor's suggested further reading in BioEssays: Pairing phosphoinositides with calcium ions in endolysosomal dynamics Abstract. (shrink)