The 44kDa Pim-1 kinase directly interacts with tyrosine kinase Etk/BMX and protects human prostate cancer cells from apoptosis induced by chemotherapeutic drugs

Y. Xie, K. Xu, B. Dai, Z. Guo, T. Jiang, H. Chen, Y. Qiu

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Protein kinase Pim-1 has been implicated in the development of hematopoietic and prostatic malignancies. Here, we present the evidence that two isoforms, the 44 and 33 kDa Pim-1, are expressed in all human prostate cancer cell lines examined. The subcellular localization of human 44 kDa Pim-1 is primarily on the plasma membrane, while the 33 kDa isoform is present in both the cytosol and nucleus in PCA cells. The 44 kDa Pim-1 contains the proline-rich motif at the N-terminus and directly binds to the SH3 domain of tyrosine kinase Etk. Such interaction leads to the activation of Etk kinase activity possibly by competing with the tumor suppressor p53. This is corroborated by the fact that overexpression of the 44 kDa Pim-1 in prostate cancer cells confers the resistance to chemotherapeutic drugs. Our results suggest that these two isoforms of Pim-1 kinase may regulate distinct substrates and the 44 kDa Pim-1 may play a more prominent role in drug resistance in prostate cancer cells.

Original languageEnglish
Pages (from-to)70-78
Number of pages9
JournalOncogene
Volume25
Issue number1
DOIs
Publication statusPublished - Jan 5 2006
Externally publishedYes

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Proto-Oncogene Proteins c-pim-1
Protein-Tyrosine Kinases
Prostatic Neoplasms
Protein Isoforms
Apoptosis
Pharmaceutical Preparations
Passive Cutaneous Anaphylaxis
src Homology Domains
Hematologic Neoplasms
Drug Resistance
Proline
Cytosol
Protein Kinases
Phosphotransferases
Cell Membrane
Cell Line
Neoplasms

Keywords

  • Apoptosis
  • Cancer
  • Kinase
  • Phosphorylation
  • Signal transduction

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

The 44kDa Pim-1 kinase directly interacts with tyrosine kinase Etk/BMX and protects human prostate cancer cells from apoptosis induced by chemotherapeutic drugs. / Xie, Y.; Xu, K.; Dai, B.; Guo, Z.; Jiang, T.; Chen, H.; Qiu, Y.

In: Oncogene, Vol. 25, No. 1, 05.01.2006, p. 70-78.

Research output: Contribution to journalArticle

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AU - Qiu, Y.

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