Phyllis C Harbor

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Glioblastoma multiforme (GBM), the most common and malignant central nervous system tumor in humans, is highly proliferative and resistant to apoptosis. Stat3, a latent transcription factor being activated by aberrant cytokine or growth factor signaling, acts as a suppressor of apoptosis in a number of cancer cells. Here we report that GBM tumors and cell(More)
Binding of interleukin (IL)-4 to its transmembrane receptor results in the Jak-mediated tyrosine phosphorylation of a number of protein components of the IL-4 signaling cascade, including Jak1, Jak2, Jak3, Tyk2, IL-4Ralpha, IRS-1, IRS-2, and Stat6 in appropriate cell types. However, the protein-tyrosine phosphatases (PTPs) that dephosphorylate these(More)
RATIONALE Heritable pulmonary arterial hypertension (HPAH) is primarily caused by mutations of the bone morphogenetic protein (BMP) type-II receptor (BMPR2). Recent identification of mutations in the downstream mediator Smad-8 (gene, SMAD9) was surprising, because loss of Smad-8 function in canonical BMP signaling is largely compensated by Smad-1 and -5. We(More)
Interleukin (IL)-4 and IL-13 share the type II IL-4 receptor for cell signaling. We show that despite expressing the necessary signaling components, glioblastoma cells failed to respond to either IL-4 or IL-13. This was in part because of the expression of a high-affinity IL-13-binding transmembrane protein IL-13R(alpha)2 that inhibited IL-13-mediated Stat6(More)
Glioblastoma multiforme (GBM) cells frequently harbor amplification and/or gain-of-function mutation of the EGFR gene leading to the activation of multiple signaling pathways. Blockade of EGFR activation inhibited the activation of both AKT and Stat3 in U87 and D54 GBM cells and induced spontaneous apoptosis, which were associated with reduction in the(More)
Suppressor of cytokine signaling (SOCS) family proteins were originally identified as cytokine-induced negative regulators of cytokine signaling. We show that SOCS-1 and SOCS-3 inhibit interleukin (IL)-4-dependent signal transducer and activator of transcription 6 (Stat6) activation of and subsequent gene induction. By contrast, SOCS-2 and(More)
PURPOSE Wilms' tumor is a childhood cancer of the kidney with an incidence of approximately 1 in 10,000. Cooccurrence of Wilms' tumor with 2q37 deletion syndrome, an uncommon constitutional chromosome abnormality, has been reported previously in three children. Given these are independently rare clinical entities, we hypothesized that 2q37 harbors a tumor(More)
In response to interleukin-4 (IL-4) or IL-13 stimulation of cells, Stat6 becomes phosphorylated on Tyr(641) and forms homodimers that migrate to the nucleus, bind to cognate DNA elements, and drive the transcription of target genes. Here, we show that phosphorylation of multiple serine residues ablates its DNA-binding activity in IL-4 stimulated cells. The(More)
Purpose: Wilms' tumor is a childhood cancer of the kidney with an incidence of ∼1 in 10,000. Cooccurrence of Wilms' tumor with 2q37 deletion syndrome, an uncommon constitutional chromosome abnormality, has been reported previously in three children. Given these are independently rare clinical entities, we hypothesized that 2q37 harbors a tumor suppressor(More)
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