Publication details

The Role of AKT and RAFTK in Beta1 Integrin Mediated Survival of Precursor B-acute Lymphoblastic Leukemia Cells



Year of publication 2002
Type Article in Periodical
Magazine / Source Leukemia and Lymphoma
MU Faculty or unit

Faculty of Medicine

Field Oncology and hematology
Keywords Integrin; Leukemia; Kinase; Adhesion
Description In this study, we report that the related adhesion focal tyrosine kinase RAFTK, is an upstream kinase in 1 integrin mediated activation of Akt. Stimulation through 1 integrins by fibronectin reversed apoptosis induced by adriamycin. Inhibitors of phosphatidylinositol 3-kinase (PI3 kinase)/Akt (LY 294002), tyrosine kinases (Herbimycin-A) and the cytotoxic agent adriamycin induced apoptosis of REH cells. 1 integrin ligation induced activation of Akt, and tyrosine phosphorylation of RAFTK and FAK, but not SYK in REH cells. This suggested that RAFTK and FAK activation might be linked to Akt activation. Evidence that RAFTK is a modulator of Akt came from phorbol myristic acetate (PMA) stimulation. RAFTK and Akt were activated but FAK was not. Using fibroblasts from FAK -/ -mice, which express high levels of RAFTK, fibronectin plating enhanced Akt activation. Pretreatment of REH cells with a PI3 kinase/Akt inhibitor LY 294002 did not inhibit RAFTK tyrosine phosphorylation showing that RAFTK is upstream of PI3k/Akt. Further evidence for a link between RAFTK tyrosine phosphorylation and Akt activation was the observation that the p85 subunit of PI3 kinase associated with RAFTK following integrin ligation in REH cells. These results suggest that RAFTK plays an anti-apoptotic role through the activation of Akt.

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