v-Abl signaling disrupts SOCS-1 function in transformed pre-B cells

Mol Cell. 2004 Aug 13;15(3):329-41. doi: 10.1016/j.molcel.2004.06.041.


The v-Abl oncogene activates Jak-Stat signaling during transformation of pre-B cells in mice. Disrupting Jak activation by deleting the Jak binding domain of v-Abl or by expressing a dominant-negative Jak1 decreases v-Abl transformation efficiency. As SOCS-1 is a known potent inhibitor of Jak kinases, the mechanism by which v-Abl bypasses SOCS-1 regulation to constitutively activate Jak kinases was investigated. SOCS-1 is expressed in v-Abl-transformed cells but is unable to inhibit v-Abl-mediated Jak-Stat signaling. In v-Abl transformants, SOCS-1 can inhibit cytokine signals, but it is more efficient at doing so when the cells are treated with STI571, an Abl kinase inhibitor. Downstream effects of v-Abl signaling include phosphorylation of SOCS-1 on nontyrosine residues, disruption of the interaction between SOCS-1 and the Elongin BC complex, and inhibition of SOCS-1-mediated proteasomal targeting of activated Jaks. These findings reveal a mechanism by which Jak-dependent oncogenes may bypass SOCS-1 inhibition.

Publication types

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

MeSH terms

  • Animals
  • B-Lymphocytes / metabolism*
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology
  • Carrier Proteins / metabolism*
  • Cell Transformation, Neoplastic / metabolism*
  • Cell Transformation, Neoplastic / pathology
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Mice
  • Mutation
  • Oncogene Proteins v-abl / genetics
  • Oncogene Proteins v-abl / metabolism*
  • Protein-Tyrosine Kinases / metabolism
  • Repressor Proteins / metabolism*
  • Signal Transduction / physiology*
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins


  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Oncogene Proteins v-abl
  • Repressor Proteins
  • SOCS1 protein, human
  • Socs1 protein, mouse
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Protein-Tyrosine Kinases