TEL-JAK2 致癌基因在血癌生成機轉的訊息傳遞路徑
Date Issued
2000
Date
2000
Author(s)
周獻堂
DOI
892314B002055
Abstract
The JAK/STAT (Janus protein tyrosine kinase/Signal
Transducers and Activators of Transcription) pathway
has emerged as a major signal transduction
mechanism in hematopoietic system, linking cell
surface receptors on the membrane to transcriptional
events in the nucleus. This pathway plays critical roles
in transducing growth and differentiation signals
emanating from ligand-activated cytokine receptor
complexes. It was demonstrated that all the cytokines
that utilize receptors of the cytokine receptor
superfamily were capable of activating members of
the JAK tyrosine kinase family.
The importance of the JAK/STAT pathway in cytokine
signaling for the hematopoietic cells suggests a
potential role in the pathogenesis of hematological
malignancies. Some evidences have supported this
hypothesis. The TEL-Jak2 fusion oncogene has
recently been found in 3 leukemia patients. The
oligomerization by the PNT domain of TEL leads to
constitutive activation ( phosphorylation) of the Jak2
tyrosine kinase domain, which is necessary for cellular
transformation.
The constitutive tyrosine phosphorylation of the
tyrosine kinase domain of TEL-Jak2 plays the critical
role for the leukemogenesis. To try to find the downstream
substrate of the TEL-Jak2 is very important for
the understanding the signal transduction pathway for
the leukemogenesis. We have constructed the hTELmJAK2
oncogene including the human TEL-specific
oligomerization domain and the catalytic domain of
murine JAK2. And our data also showed the TELinduced
oligomerization of TEL-JAK2 resulted in the
constitutive activation of its tyrosine kinase activity
and conferred cytokine (IL-3)-independent
proliferation to the IL-3-dependent Ba/F3
hematopoietic cell line. We have also identified one
strongly constitutively tyrosine-phosphorylated
protein in the Ba/F3/TEL-JAK2 cells which is not
found in the Ba/F3 parent cells by using the character
of the constitutively activated catalytic activity of
TEL-JAK2. We are studying the biological character
of this down-stream substrate of TEL-JAK2 oncogene
to elucidate the signal transduction pathway for
leukemogenesis in the hematopoietic system.
Publisher
臺北市：國立臺灣大學醫學院小兒科
Type
report
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