Phosphoinositide 3-kinase and Bruton's tyrosine kinase regulate overlapping sets of genes in b lymphocytes

David A. Fruman, Gregory Z. Ferl, Sam S. An, Amber C. Donahue, Anne B. Satterthwaite, Owen N. Witte

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Bruton's tyrosine kinase (Btk) acts downstream of phosphoinositide 3-kinase (P13K) in a pathway required for B cell receptor (BCR)-dependent proliferation. We used DNA microarrays to determine what fraction of genes this pathway influences and to investigate whether P13K and Btk mediate distinct gene regulation events. As complete loss-of-function mutations in P13K and Btk alter B cell subpopulations and may cause compensatory changes in gene expression, we used B cells with partial loss of function in either P13K or Btk. Only about 5% of the BCR-dependent gene expression changes were significantly affected by reduced P13K or Btk. The results indicate that P13K and Btk share target genes, and that P13K influences additional genes independently of Btk. These data are consistent with P13K acting through Btk and other effectors to regulate expression of a critical subset of BCR target genes that determine effective entry into the cell cycle.

Original languageEnglish (US)
Pages (from-to)359-364
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number1
DOIs
StatePublished - Jan 8 2002

ASJC Scopus subject areas

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