• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Tec and Jak2 kinases cooperate to mediate cytokine-driven activation of c-fos transcription.

Although transcriptional activation of the c-fos proto-oncogene plays an intrinsic role in the mechanism of blood cell growth, it is still obscure how protein-tyrosine kinases (PTKs) regulate the cytokine-driven c-fos activation pathway. We present here that Tec PTK is tyrosine-phosphorylated and activated by granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulation in a human GM-CSF-dependent cell line. Moreover, we could show that introduction of Tec into mouse BA/F3-hGMRalphabeta cells can profoundly activate the c-fos promoter in response to GM-CSF or to interleukin-3 (IL-3). In contrast, introduction of a kinase-deleted Tec could suppress cytokine-driven c-fos activation, indicating that Tec is directly involved in the regulation of c-fos transcription. Interestingly, strong activation by Tec of the c-fos promoter was blocked by the co-expression of dominant negative Jak2. The molecular interaction between Tec and Jak2 was then investigated both in mammalian and insect cell systems, revealing that they can not only bind to each other, but either of the two can phosphorylate the other. Thus, Tec and Jak2 can "cross-talk" in a complexed way to mediate cytokine-driven c-fos activation.

Pubmed ID: 9473212

Authors

  • Yamashita Y
  • Watanabe S
  • Miyazato A
  • Ohya Ki
  • Ikeda U
  • Shimada K
  • Komatsu N
  • Hatake K
  • Miura Y
  • Ozawa K
  • Mano H

Journal

Blood

Publication Data

March 1, 1998

Associated Grants

None

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Baculoviridae
  • Cell Line
  • Gene Expression
  • Genes, fos
  • Genes, ras
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Humans
  • Interleukin-3
  • Janus Kinase 2
  • Mice
  • Phosphorylation
  • Phosphotyrosine
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • Recombinant Proteins
  • Signal Transduction
  • Spodoptera
  • Transcription, Genetic