SHIP2 overexpression strongly reduces the proliferation rate of K562 erythroleukemia cell line

SHIP2 controls plasma membrane PI(4,5)P2 thereby participating in the control of cell migration in 1321 N1 glioblastoma cells

“…We conclude that in N1 cells, SHIP2 controls the balance between PI(4,5)P2 and PI4P at the plasma membrane consistent with its previously established catalytic activity towards PI(4,5)P2 in vitro (Giuriato et al, 2002;Nakatsu et al, 2010;Taylor et al, 2000;Vandeput et al, 2007). In addition, it is involved in controlling the PI(3,4,5)P3-PI(3,4)P2 balance in lamellipodia.…”

“…SHIP2 also regulates important biological mechanisms such as cell adhesion (Prasad et al, 2002), migration (Yu et al, 2010) or endocytosis at the leading edge of the cells (Boucrot et al, 2015). It is accepted that PI(3,4,5)P3 is the main SHIP2 substrate (Giuriato et al, 2002;Nakatsu et al, 2010;Taylor et al, 2000) and its reaction product phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2] is a lipid involved in endocytosis, lamellipodia formation (Krause and Gautreau, 2014), invadopodium maturation (Sharma et al, 2013) and ruffle formation (Hasegawa et al, 2011). In addition to PI(3,4,5)P3, PI(4,5)P2 is also a substrate of SHIP2 although evidence of this in intact cells has been more difficult to establish, although it has been observed in a very few models, e.g.…”

Inhibition of Abl tyrosine kinase enhances nerve growth factor-mediated signaling in Bcr–Abl transformed cells via the alteration of signaling complex and the receptor turnover

“…We show here that the SHIP2/ CrkL/Bcr-Abl complex was not detected after imatinib treatment; however, TrkA activation did not cause SHIP2 phosphorylation. At present, the role of SHIP2 in K562 cells is not clear; however, in these cells, it has been shown that SHIP2 reduces the proliferation rate (Giuriato et al, 2002), suggesting that the dephosphorylation of SHIP2 may participate in imatinibmediated enhancement of TrkA signaling. We also present here a second mechanism, in which imatinib treatment influences receptor internalization.…”

mTOR, A New Therapeutic Target in Acute Myeloid Leukemia

“…When transfected in both K562 and U937 cell lines, the SHIP V684E mutant with decreased phosphatase activity, protected leukemic cells from serum starvation or etoposide-mediated apoptosis. 105,106 Thus, accumulating evidence shows that the dysregulation of phosphatase activity could play a role in leukemogenesis. However, it is currently not known whether SHP-1 or SHIP-deficient AML cells are sensitive to mTOR inhibition by rapamycin.…”