Functional involvement of Akt signaling downstream of Jak1 in v-Abl-induced activation of hematopoietic cells

Blood. 2002 Aug 1;100(3):966-73. doi: 10.1182/blood.v100.3.966.


Activation of intracellular signaling pathways is important for cellular transformation and tumorigenesis. The nonreceptor tyrosine kinases Jak1 and Jak3, which bind to the v-Abl oncoprotein, are constitutively activated in cells transformed with the Abelson murine leukemia virus. A mutant of p160 v-Abl lacking the Jak1-binding region (v-Abl Delta858-1080) has a significant defect in Jak/STAT (signal transducers and activators of transcription) activation, cytokine-independent cell growth/survival, and tumorigenesis. To identify the pathways downstream of Jak kinases in v-Abl-mediated signaling, we examined the activation of several signaling molecules by p160 v-Abl or the v-Abl Delta858-1080 mutant. We demonstrate that, in addition to the decreased Ras activation, signaling through phosphatidylinositol-3 kinase and Akt are impaired in cells expressing mutant v-Abl. The proliferative defect of v-Abl Delta858-1080 was rescued by activated v-Akt and was also moderately rescued by activated v-H-Ras. However, constitutive active phosphatidylinositol-3 kinase (p110CAAX) did not complement this effect. Cells expressing v-Abl Delta858-1080 demonstrated reduced tumor formation in nude mice. In contrast, cells coexpressing v-Akt with v-Abl Delta858-1080 demonstrated reduced latency and increased frequency of tumor formation in nude nice compared with cells expressing v-Abl Delta858-1080 alone, whereas v-H-Ras or p110CAAX had minimum effects on tumor formation. These results suggest that Jak1-dependent Akt activation is important in v-Abl-mediated transformation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis
  • Binding Sites
  • Cell Line
  • Cell Transformation, Neoplastic / drug effects
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / enzymology
  • Hematopoietic Stem Cells / metabolism*
  • Janus Kinase 1
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / physiology*
  • Mice
  • Mice, Nude
  • Oncogene Proteins v-abl / administration & dosage
  • Oncogene Proteins v-abl / genetics
  • Oncogene Proteins v-abl / pharmacology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Serine-Threonine Kinases*
  • Protein-Tyrosine Kinases / metabolism
  • Protein-Tyrosine Kinases / physiology*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-akt
  • Receptor Cross-Talk
  • Sequence Deletion
  • Signal Transduction*
  • ras Proteins / metabolism


  • Oncogene Proteins v-abl
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • Jak1 protein, mouse
  • Janus Kinase 1
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • ras Proteins