Kinase requirements in human cells: I. Comparing kinase requirements across various cell types

Dorre A. Grueneberg, Sebastien Degot, Joseph Pearlberg, Wenliang Li, Joan E. Davies, Amy Baldwin, Wilson Endege, John Doench, Jacqueline Sawyer, Yanhui Hu, Frederick Boyce, Jun Xian, Karl Munger, Ed Harlow

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

shRNA loss-of-function screens were used to identify kinases that were rate-limiting for promoting cell proliferation and survival. Here, we study the differences in kinase requirements among various human cells, including freshly prepared primary cells, isogenic cells, immortalized cells, and cancer cell lines. Closely related patterns of kinase requirements among the various cell types were observed in three cases: (i) in repeat experiments using the same cells, (ii) with multiple populations of freshly prepared primary epithelial cells isolated from the same tissue source, and (iii) between nearly isogenic cells that differ from each other by the expression of a single gene. Other commonly used cancer cell lines were distinct from one another, even when they were isolated from similar tumor types. Even primary cells of different lineages isolated from the same tissue source showed many differences. The differences in kinase requirements among cell lines observed in this study suggest that the control of proliferation and survival may be significantly different between cell lines and that simple comparisons from any one cell to another may be misleading. Although the regulation of cell proliferation and survival are heavily studied areas, we did not see a bias in these screens toward the identification of previously known and well studied kinases, suggesting that our knowledge of molecular events in these areas is still meager.

Original languageEnglish (US)
Pages (from-to)16472-16477
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number43
DOIs
StatePublished - Oct 28 2008
Externally publishedYes

Fingerprint

Phosphotransferases
Cell Line
Cell Survival
Cell Proliferation
Neoplasms
Cell Lineage
Small Interfering RNA
Epithelial Cells
Survival
Population
Genes

Keywords

  • Cancer
  • Essential kinases
  • Fingerprints
  • shRNA screens

ASJC Scopus subject areas

  • General

Cite this

Kinase requirements in human cells : I. Comparing kinase requirements across various cell types. / Grueneberg, Dorre A.; Degot, Sebastien; Pearlberg, Joseph; Li, Wenliang; Davies, Joan E.; Baldwin, Amy; Endege, Wilson; Doench, John; Sawyer, Jacqueline; Hu, Yanhui; Boyce, Frederick; Xian, Jun; Munger, Karl; Harlow, Ed.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 43, 28.10.2008, p. 16472-16477.

Research output: Contribution to journalArticle

Grueneberg, DA, Degot, S, Pearlberg, J, Li, W, Davies, JE, Baldwin, A, Endege, W, Doench, J, Sawyer, J, Hu, Y, Boyce, F, Xian, J, Munger, K & Harlow, E 2008, 'Kinase requirements in human cells: I. Comparing kinase requirements across various cell types', Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 43, pp. 16472-16477. https://doi.org/10.1073/pnas.0808019105
Grueneberg, Dorre A. ; Degot, Sebastien ; Pearlberg, Joseph ; Li, Wenliang ; Davies, Joan E. ; Baldwin, Amy ; Endege, Wilson ; Doench, John ; Sawyer, Jacqueline ; Hu, Yanhui ; Boyce, Frederick ; Xian, Jun ; Munger, Karl ; Harlow, Ed. / Kinase requirements in human cells : I. Comparing kinase requirements across various cell types. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 43. pp. 16472-16477.
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