Inositol 5'-phosphatase SHIP-1 (SHIP) is a negative regulator of signal transduction in haematopoietic cells. SHIP inactivation may be involved in the pathogenesis of leukaemia. An inducible expression system was combined with microarray analysis to identify target genes regulated by SHIP in the human T-cell leukaemia cell line Jurkat. One gene identified was Krüppel-like factor 2 (KLF2), which was up-regulated two to threefold at the RNA and protein level after the induced expression of SHIP. KLF2, a negative regulator of T cell proliferation, has been implicated in T cell quiescence. KLF2 or SHIP expression in Jurkat cells caused 45% or 60% reduction of proliferation, respectively. SHIP can up-regulate KLF2 expression, implicating KLF2 in the SHIP-mediated growth inhibition of a human leukaemic T-cell line.
