title: Tumor suppression by phospholipase C-beta3 via SHP-1-mediated dephosphorylation of Stat5.
abstract: 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-beta3-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-beta3 deficiency was suggested in mouse lymphomas in PLC-beta3(-/-) and in Emicro-myc;PLC-beta3(+/-) 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-beta3 is likely a tumor suppressor.
authors: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
authors: Wenbin
authors: W
authors: Xiao
authors: Hong
authors: H
authors: Hong
authors: Yuko
authors: Y
authors: Kawakami
authors: Yuko
authors: Y
authors: Kato
authors: Dianqing
authors: D
authors: Wu
authors: Hiroki
authors: H
authors: Yasudo
authors: Akiko
authors: A
authors: Kimura
authors: Hiromi
authors: H
authors: Kubagawa
authors: Luigi F
authors: LF
authors: Bertoli
authors: Randall S
authors: RS
authors: Davis
authors: Luan A
authors: LA
authors: Chau
authors: Joaquin
authors: J
authors: Madrenas
authors: Cyrus C
authors: CC
authors: Hsia
authors: Anargyros
authors: A
authors: Xenocostas
authors: Thomas J
authors: TJ
authors: Kipps
authors: Lothar
authors: L
authors: Hennighausen
authors: Atsushi
authors: A
authors: Iwama
authors: Hiromitsu
authors: H
authors: Nakauchi
authors: Toshiaki
authors: T
authors: Kawakami
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D054799:Phospholipase C beta / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D050799:STAT5 Transcription Factor; D025521:Tumor Suppressor Proteins; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; C509248:Ptpn6 protein, mouse; D054799:Phospholipase C beta