Tumor Suppression by Phospholipase C- beta 3 via SHP-1-Mediated Dephosphorylation of Stat5

• Published in: Cancer cell Vol. 16; no. 2; pp. 161 - 171
• Main Authors: Xiao, W, Hong, H, Kawakami, Y, Kato, Y, Wu, D, Yasudo, H, Kimura, A, Kubagawa, H, Bertoli, L F, Davis, R S, Chau, LA, Madrenas, J, Hsia, C C, Xenocostas, A, Kipps, T J, Hennighausen, L, Iwama, A, Nakauchi, H, Kawakami, T
• Format: Journal Article
• Language: English
• Published: 04.08.2009
• ISSN: 1535-6108
• DOI: 10.1016/j.ccr.2009.05.018

Given its catalytic activity to generate diacylglycerol and inositol 1,4,5-trisphosphate, phospholipase C (PLC) is implicated in promoting cell growth. However, we found that PLC- beta 3-deficient mice develop myeloproliferative disease, lymphoma, and other tumors. The mutant mice have increased numbers of hematopoietic stem cells with increased proliferative, survival, and myeloid-differentiative abilities. These properties are dependent on Stat5 and can be antagonized by the protein phosphatase SHP-1. Stat5-dependent cooperative transformation by active c-Myc and PLC- beta 3 deficiency was suggested in mouse lymphomas in PLC- beta 3 super(-) super( )/ super(-) and in E mu -myc; PLC- beta 3 super(+) super(/) super(-) mice and human Burkitt's lymphoma cells. The same mechanism for malignant transformation seems to be operative in other human lymphoid and myeloid malignancies. Thus, PLC- beta 3 is likely a tumor suppressor.