Lymphocyte Signaling

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SH2-containing inositol phosphatase 1 (SHIP1) is a hematopoietic phosphatase that hydrolyzes phosphatidylinositol-3,4,5-triphosphate to phosphatidylinositol-3,4-bisphosphate (1). SHIP1 is a cytosolic phosphatase with an SH2 domain in its amino terminus and two NPXY Shc binding motifs in its carboxy terminus (1,2). Upon receptor cross-linking, SHIP is first recruited to the membrane junction through binding of its SH2 domain to the phospho-tyrosine in the ITIM motif (2), followed by tyrosine phosphorylation on the NPXY motif (2). The membrane relocalization and phosphorylation on the NPXY motif is essential for the regulatory function of SHIP1 (3-5). Its effect on calcium flux, cell survival, growth, cell cycle arrest and apoptosis is mediated through the PI3K and Akt pathways (3-5). Tyr1021 is located in one of the NPXY motifs in SHIP1, and its phosphorylation is important for SHIP1 function (6).

SHIP2, a homolog of SHIP1, is highly expressed in heart, skeletal muscle and placenta (7). SHIP2 negatively regulates insulin signaling (8) and polymorphisms in SHIP2 have been linked to hyperglycemia (9). Recent studies also suggest SHIP2 as a therapeutic target for the treatment of both obesity and type 2 diabetes (10,11). Tyr986 and Tyr987 are phosphorylated upon PDGF treatment of 3T3-L1 cells. Phosphorylation of these residues has also been observed in human cancer cells (12-15).

1. Tridandapani, S. et al. (1997) Mol Cell Biol 17, 4305-11.
2. Liu, L. et al. (1997) J Biol Chem 272, 8983-8.
3. Malbec, O. et al. (2001) J Biol Chem 276, 30381-91.
4. Carver, D.J. et al. (2000) Blood 96, 1449-56.
5. Scharenberg, A.M. et al. (1998) EMBO J 17, 1961-72.
6. Sattler, M. et al. (2001) J Biol Chem 276, 2451-8.
7. Pesesse, X. et al. (1997) Biochem Biophys Res Commun 239, 697-700.
8. Wada, T. et al. (2001) Mol Cell Biol 21, 1633-46.
9. Ishida, S. et al. (2006) Pancreas 33, 63-7.
10. Dyson, J.M. et al. (2005) Int J Biochem Cell Biol 37, 2260-5.
11. Sasaoka, T. et al. (2006) Pharmacol Ther 112, 799-809.
12. Artemenko, Y. et al. (2007) J Cell Physiol 211, 598-607.
13. Goss, V.L. et al. (2006) Blood 107, 4888-97.
14. Rikova, K. et al. (2007) Cell 131, 1190-203.
15. Guo, A. et al. (2008) Proc Natl Acad Sci USA 105, 692-7.

• Luo, Y. et al. (2009) Cell Signal 21, 1370-8. Applications: Western Blotting

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Phospho-SHIP2 (Tyr986/987) Antibody

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