DISSECTING THE INTERFACE BETWEEN SIGNALING AND TRANSCRIPTIONAL REGULATION IN HUMAN B CELLS

Pacific Symposium on Biocomputing 2009

KAI WANG ; MARIANO J. ALVAREZ ; BRYGIDA C. BISIKIRSKA ; RUNE LINDING ; KATIA BASSO ; RICCARDO DALLA FAVERA ; ANDREA CALIFANO

Others  :  http://psb.stanford.edu/psb-online/proceedings/psb09/wang.pdf
PID  :  19874

来源: CEUR

【 摘 要 】

A key role of signal transduction pathways is to control transcriptional programs in thenucleus as a function of signals received by the cell via complex post-translationalmodification cascades. This determines cell-context specific responses to environmentalstimuli. Given the difficulty of quantitating protein concentration and post-translationalmodifications, signaling pathway studies are still for the most part conducted oneinteraction at the time. Thus, genome-wide, cell-context specific dissection of signalingpathways is still an open challenge in molecular systems biology.In this manuscript we extend the MINDy algorithm for the identification of post- translational modulators of transcription factor activity, to produce a first genome-widemap of the interface between signaling and transcriptional regulatory programs in humanB cells. We show that the serine-threonine kinase STK38 emerges as the most pleiotropicsignaling protein in this cellular context and we biochemically validate this finding byshRNA-mediated silencing of this kinase, followed by gene expression profile analysis.We also extensively validate the inferred interactions using protein-protein interactiondatabases and the kinase-substrate interaction prediction algorithm NetworKIN.