What question did this study set out to answer?

Investigate additional intracellular signaling pathways engaged by the TEL-JAK2 fusion oncoprotein beyond STAT activation to clarify mechanisms of leukemogenesis.

August 15, 2002Blood

TEL-JAK2 constitutively activates the extracellular signal-regulated kinase (ERK), stress-activated protein/Jun kinase (SAPK/JNK), and p38 signaling pathways.

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Authors

JHJenny HoWestern University MNMelody H.-H. NguyenOntario Institute for Cancer Research JDJamil DierovUniversity of Pennsylvania

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Implication

In vitro study reveals constitutive activation of ERK, SAPK/JNK, and p38 by TEL-JAK2 in Ba/F3 cells, indicating that ERK signaling mediates leukemogenic factor independence.

Key Points

Investigate additional intracellular signaling pathways engaged by the TEL-JAK2 fusion oncoprotein beyond STAT activation to clarify mechanisms of leukemogenesis.
Expressed wild-type TEL-JAK2 isoforms and a Tyr314Phe binding mutant in Ba/F3 hematopoietic cells to assess adaptor recruitment and Ras activation.
Assayed phosphorylation levels of ERK1/2, SAPK/JNK, and p38 across TEL-JAK2 variants.
Tested the effects of chemical inhibitors of ERK1/2, SAPK/JNK, and p38 on growth factor independence.
TEL-JAK2 induced constitutive tyrosine phosphorylation of Shc and Ship-1, while the Tyr314Phe mutation reduced Grb2 association and decreased Ras activation.
All TEL-JAK2 isoforms activated SAPK/JNK and phosphorylated p38, whereas TEL-JAK2(5-12) and (5-19) preferentially stimulated ERK2 phosphorylation compared with TEL-JAK2(4-17).
Pharmacological inhibition of ERK1/2 abolished TEL-JAK2(5-19)-mediated factor independence in Ba/F3 cells, whereas inhibition of SAPK/JNK or p38 had no effect.

Cite This Study

Ho et al. (2002) studied this question.

synapsesocial.com/papers/6a706c1826a7f98052dcec8f https://doi.org/10.1182/blood.v100.4.1438.h81602001438_1438_1448

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Implication

In vitro study reveals constitutive activation of ERK, SAPK/JNK, and p38 by TEL-JAK2 in Ba/F3 cells, indicating that ERK signaling mediates leukemogenic factor independence.

TEL-JAK2 constitutively activates the extracellular signal-regulated kinase (ERK), stress-activated protein/Jun kinase (SAPK/JNK), and p38 signaling pathways.

Discussion

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Implication

Key Points

Cite This Study

TEL-JAK2 constitutively activates the extracellular signal-regulated kinase (ERK), stress-activated protein/Jun kinase (SAPK/JNK), and p38 signaling pathways.

Discussion

Member takes

Implication

Key Points

Cite This Study

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