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- Discovery of SHIP1/2 in a complex of tyrosine phosphorylated proteins
- Tumour suppressor PTEN is critical in lowering the level of PtdIns(3,4,5)P3 and the Akt pathway, whereas SHIPs may play a dual role
- SHIP1/2 function: Lessons from knockout mice
- Reversible Ser/Thr phosphorylation of SHIP could be critical in targeting the enzyme
- SHIP1 and SHIP2 substrate specificity: More than one substrate in vivo?
- Is SHIP1/2 tyrosine phosphorylation an index of enzymatic activation?
- SYNJ1 and SHIP1 phosphorylation on Ser residues
- SHIP2 phosphorylation on T958 and S132 and other phosphosites
- Regulating SHIP2 Ser/Thr phosphorylation: SHIP2 interaction with PP2A
- Interactome of SHIP1/2 and its influence on function and signalling
- A model of SHIP2 targeting to the plasma membrane or to the nucleus
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