Reciprocal regulation of Abl kinase by Crk Y251 and Abi1 controls invasive phenotypes in glioblastoma

Sushil Kumar, Bin Lu, Updesh Dixit, Sajjad Hossain, Yongzhang Liu, Jing Li, Peter Hornbeck, Weiming Zheng, Adam G. Sowalsky, Leszek Kotula, Raymond B. Birge

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Crk is the prototypical member of a class of Src homology 2 (SH2) and Src homology 3 (SH3) domain-containing adaptor proteins that positively regulate cell motility via the activation of Rac1 and, in certain tumor types such as GBM, can promote cell invasion and metastasis by mechanisms that are not well understood. Here we demonstrate that Crk, via its phosphorylation at Tyr251, promotes invasive behavior of tumor cells, is a prominent feature in GBM, and correlating with aggressive glioma grade IV staging and overall poor survival outcomes. At the molecular level, Tyr251 phosphorylation of Crk is negatively regulated by Abi1, which competes for Crk binding to Abl and attenuates Abl transactivation. Together, these results show that Crk and Abi1 have reciprocal biological effects and act as a molecular rheostat to control Abl activation and cell invasion. Finally, these data suggest that Crk Tyr251 phosphorylation regulate invasive cell phenotypes and may serve as a biomarker for aggressive GBM.

Original languageEnglish (US)
Pages (from-to)37792-37807
Number of pages16
Issue number35
StatePublished - 2015
Externally publishedYes


  • Abi1
  • Cell Invasion
  • Glioblastoma multiformae
  • Non canonical Crk signaling

ASJC Scopus subject areas

  • Oncology


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