The role of phosphotyrosine phosphatases in haematopoietic cell signal transduction

Frearson, Julie A.; Alexander, Denis R.

doi:10.1002/bies.950190509

Cited by 68 publications

(44 citation statements)

References 83 publications

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“…The genes in Group 1 included a number of protein phosphatases that may act to down-regulate signal transduction pathways that promote cell growth, 56 TGF-␤1, a potent inhibitor of cellular proliferation, 57 and endoglin, a member of the TGF-␤ superfamily of receptors. 58 The genes in Group 1 of Table 4 also include two members of the AP-1 (activating protein-1) family of transcription factors that con- sists of homodimers and heterodimers of Jun (v-Jun, c-Jun, JunB, JunD), Fos (v-Fos, c-Fos, FosB, Fra1, Fra2), Jun dimerization partners (JDP1 and JDP2), or activating transcription factor (ATF2, ATF3, B-ATF) proteins.…”

Section: Expression Profiling Of T(14;18)-positive Cell Lines 131mentioning

confidence: 99%

Microarray Analysis of B-Cell Lymphoma Cell Lines with the t(14;18)

Robetorye

Bohling

Morgan

et al. 2002

The Journal of Molecular Diagnostics

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The t(14;18) is the most common genetic alteration in follicular lymphoma, and is detectable in a subset of diffuse large B-cell lymphomas (DLBCL), resulting in over-expression of the anti-apoptotic protein BCL-2. Although the t(14;18)-induced over-expression of BCL-2 is an important step in lymphomagenesis,The t(14;18) is a frequent chromosomal alteration in nonHodgkin's lymphomas (NHL), occurring in up to 90% of follicular lymphomas 1 and 20 to 30% of diffuse large B-cell lymphomas (DLBCL). 2,3 This translocation is acquired early in B-cell development and results in juxtaposition of the bcl-2 gene on chromosome 18 with the immunoglobulin heavy-chain locus on chromosome 14, resulting deregulated expression of a structurally intact BCL-2 protein. 4 -8 BCL-2 is located in the inner mitochondrial membrane and functions as an anti-apoptotic protein that inhibits programmed cell death, 9 resulting in accumulation of B-lymphocytes by virtue of increased cell survival. 9 -11 Although the t(14;18)-induced over-expression of bcl-2 is an important step in lymphomagenesis, this alteration alone is not sufficient to produce malignant lymphoma. This has been demonstrated in in vitro gene transfer experiments using cell lines and transgenic mice studies in which forced over-expression of bcl-2 was insufficient to cause lymphoma. 12,13 Indeed, low numbers of t(14; 18)-carrying cells can be detected in benign lymphoid tissues such as follicular hyperplasias and the hyperplastic tonsils of young children. 14 These studies indicate that cumulative genetic and cellular alterations superimposed on the t(14;18) are necessary for the development of lymphoma and underscore the need for further analysis of t(14;18)-containing DLBCLs to identify additional genes involved in lymphomagenesis and progression.cDNA microarray technology allows large scale parallel analyses of gene expression and permits simultaneous comparison of the relative gene expression levels of several thousand genes in different cell types. 15,16 This approach has now been used successfully by a number

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Section: Expression Profiling Of T(14;18)-positive Cell Lines 131mentioning

confidence: 99%

Microarray Analysis of B-Cell Lymphoma Cell Lines with the t(14;18)

Robetorye

Bohling

Morgan

et al. 2002

The Journal of Molecular Diagnostics

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“…Their function is mediated by transmembrane receptors that transduce intracellular signals through the engagement and activation of cytoplasmic e ectors molecules. The duration and intensity of cytokine-induced signals are regulated by protein tyrosine phosphatases (Frearson and Alexander, 1997;Siminovitch and Neel, 1998), phosphatidyl inositol lipid phosphatases (Krystal, 2000;Rohrschneider et al, 2000), and by the induction the SOCS-family of JAK kinase pseudosubstrate inhibitors (Endo et al, 1997;Naka et al, 1997Naka et al, , 1999Starr and Hilton, 1999;Starr et al, 1997;Yasukawa et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

The tumor suppressor activity of SOCS-1

et al. 2002

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SOCS-1 is an inducible SH2-containing inhibitor of Jak kinases and as such can potently suppress cytokine signaling. SOCS-1 de®cient mice die within the ®rst three weeks of life from a myeloproliferative disorder driven by excessive interferon signaling. We report here that SOCS-1 inhibits proliferation signals induced by a variety of oncogenes active within the hematopoietic system. Ectopic expression of SOCS-1 abolished proliferation mediated by a constitutively active form of the KIT receptor, TEL-JAK2, and v-ABL, and reduced metastasis from BCR-ABL transformed cells. SOCS-1, however, did not interfere with v-SRC or RASV12 mediated cellular transformation. A mutant form of SOCS-1 unable to bind through its SH2 domain to tyrosine phosphorylated proteins could still inhibit KIT, but not TEL-JAK2, indicating multiple mechanisms for SOCS-1-mediated tumor suppression. We show that the steady state levels of TEL-JAK2 and to a greater extent v-ABL are diminished in the presence of SOCS-1. Lastly, we show that SOCS-1 7/7 ®broblasts are more sensitive than wild type ®broblasts to either spontaneous or oncogene-induced transformation. These data suggest that loss-of-function of SOCS-1 may collaborate with a variety of hematopoietic oncogenes to facilitate tumor progression.

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“…PTPases of this class, generally those containing SH2 domains, have been found associated with receptor-type PTKs as well as with receptors devoid of PTK activity. Depending on their context, associations of this type can enhance or decrease the intensity of the transduced signal and are physiologically signi®cant (Tonks and Neel, 1996;Frearson and Alexander, 1997;Neel and Tonks, 1997).…”

Section: Introductionmentioning

confidence: 99%

Protein tyrosine phosphatase ε increases the risk of mammary hyperplasia and mammary tumors in transgenic mice

Elson

1999

Oncogene

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Accurate phosphorylation of tyrosine residues in proteins plays a central role in regulation of cellular function. Although connections between aberrant tyrosine kinase activity and malignancy are well-established, signi®cantly less is known about the roles of protein tyrosine phosphatases (PTPases) in tumorigenesis. We have previously shown that the transmembranal form of PTPase Epsilon (PTPe) is upregulated in mouse mammary tumors initiated speci®cally by ras or neu, suggesting that PTPe may play a role in transformation by these two oncogenes. In order to test this notion in vivo, we created transgenic mice that express elevated levels of PTPe in their mammary epithelium by use of the MMTV promoter/enhancer. Following several cycles of pregnancy female MMTV-PTPe mice uniformly developed pronounced and persistent mammary hyperplasia which was accompanied by residual milk production. Solitary mammary tumors were often detected secondary to mammary hyperplasia. The sporadic nature of the tumors, the long latency period prior to their development, and low levels of transgene expression in the tumors indicate that PTPe provides a necessary, but insu cient, signal for oncogenesis. The results provide genetic evidence that PTPe plays an accessory role in production of mammary tumors in a manner consistent with its upregulation in mammary tumors induced by ras or neu.

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The role of phosphotyrosine phosphatases in haematopoietic cell signal transduction

Cited by 68 publications

References 83 publications

Microarray Analysis of B-Cell Lymphoma Cell Lines with the t(14;18)

Microarray Analysis of B-Cell Lymphoma Cell Lines with the t(14;18)

The tumor suppressor activity of SOCS-1

Protein tyrosine phosphatase ε increases the risk of mammary hyperplasia and mammary tumors in transgenic mice

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