The genesis of tyrosine phosphorylation.

Published in Cold Spring Harbor perspectives in biology

Tyrosine phosphorylation of proteins was discovered in 1979, but this posttranslational modification had been "invented" by evolution more than a billion years ago in single-celled eukaryotic organisms that were the antecedents of the first multicellular animals. Because sophisticated cell-cell communication is a sine qua non for the existence of m...

Psy2 targets the PP4 family phosphatase Pph3 to dephosphorylate Mth1 and repress glucose transporter gene expression.

Published in Molecular and cellular biology

The reversible nature of protein phosphorylation dictates that any protein kinase activity must be counteracted by protein phosphatase activity. How phosphatases target specific phosphoprotein substrates and reverse the action of kinases, however, is poorly understood in a biological context. We address this question by elucidating a novel function...

Mass spectrometry-based quantification of the cellular response to methyl methanesulfonate treatment in human cells

Published in DNA Repair

Translating experience: thinking outside the box.

Published in Nature cell biology

The RING finger protein RNF8 ubiquitinates Nbs1 to promote DNA double-strand break repair by homologous recombination.

Published in The Journal of biological chemistry

Ubiquitination plays an important role in the DNA damage response. We identified a novel interaction of the E3 ubiquitin ligase RNF8 with Nbs1, a key regulator of DNA double-strand break (DSB) repair. We found that Nbs1 is ubiquitinated both before and after DNA damage and is a direct ubiquitination substrate of RNF8. We also identified key residue...

The evolution of protein phosphorylation. Preface.

Published in Philosophical transactions of the Royal Society of London. Series B, Biological sciences

Why nature chose phosphate to modify proteins.

Published in Philosophical transactions of the Royal Society of London. Series B, Biological sciences

The advantageous chemical properties of the phosphate ester linkage were exploited early in evolution to generate the phosphate diester linkages that join neighbouring bases in RNA and DNA (Westheimer 1987 Science 235, 1173-1178). Following the fixation of the genetic code, another use for phosphate ester modification was found, namely reversible p...

The transcriptional coactivators p/CIP and SRC-1 control insulin resistance through IRS1 in obesity models.

Published in PloS one

Three p160 family members, p/CIP, SRC1, and TIF2, have been identified as transcriptional coactivators for nuclear hormone receptors and other transcription factors in vitro. In a previous study, we reported initial characterization of the obesity-resistant phenotypes of p/CIP and SRC-1 double knockout (DKO) mice, which exhibit increased energy exp...

Cancer-associated loss-of-function mutations implicate DAPK3 as a tumor-suppressing kinase.

Published in Cancer research

Cancer kinome sequencing studies have identified several protein kinases predicted to possess driver (i.e., causal) mutations. Using bioinformatic applications, we have pinpointed DAPK3 (ZIPK) as a novel cancer-associated kinase with functional mutations. Evaluation of nonsynonymous point mutations, discovered in DAPK3 in various tumors (T112M, D16...

Protein kinase signaling networks in cancer.

Published in Current opinion in genetics & development

Protein kinases orchestrate the activation of signaling cascades in response to extracellular and intracellular stimuli to control cell growth, proliferation, and survival. The complexity of numerous intracellular signaling pathways is highlighted by the number of kinases encoded by the human genome (539) and the plethora of phosphorylation sites i...