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Journal Club of Scientist-Recommended Papers: Oct 1, 2004


The Arabidopsis Putative G Protein¯Coupled Receptor GCR1 Interacts with the G Protein a Subunit GPA1 and Regulates Abscisic Acid Signaling

Pandey S, Assmann, S. The Plant Cell. 2004 Jun; 16: 1616-1632.

Lead author Sarah Assmann and co-author Sona Pandey, both at Penn State University, describe their attempts to investigate the interactions of G protein-coupled receptors encoded by the Arabidopsis thaliana genome. The Arabidopsis genome encodes single prototypical Ga (GPA1) and Gß (AGB1) subunits, and two probable Gg subunits (AGG1 and AGG2). One Arabidopsis gene, GCR1, encodes a protein with significant sequence similarity to nonplant GPCRs and a predicted 7-transmembrane domain structure characteristic of GPCRs. However, whether GCR1 actually interacts with GPA1 was unknown. They demonstrate by in vitro pull-down assays, by yeast split-ubiquitin assays, and by coimmunoprecipitation from plant tissue that GCR1 and GPA1 are indeed physically coupled.

Lund says this paper is important because it presents evidence that the heterotrimeric protein complex in G proteins — of which only one exists in plants — potentially functions as a receptor for abscisic acid, a major plant hormone. “This is a major breakthrough because there’s not been any really clear, definitive evidence prior as to how the ABA hormone might be perceived,” he says. The paper also suggests, Lund says, that ABA might be one of the major hormones promoting the initiation of ripening in non-climacteric plants like grapes, strawberries, and oranges, findings that could lead to new targets for genetic modifications for agricultural applications.

Steven Lund

Assistant Professor of Viticulture/Plant Genomics

The University of British Columbia

Single Cell Profiling of Potentiated Phospho-Protein Networks in Cancer Cells

Irish JM, Hovland R, Krutzik PO, Perez OD, Bruserud O, Gjertsen BT, Nolan GP. Cell. 2004 Jul 23;118(2):217-228.

In this Cell paper, lead author Garry Nolan at Stanford University and his co-authors used multiparameter flow cytometry to monitor phospho-protein responses to environmental cues in acute myeloid leukemia at the single cell level. By exposing cancer cell signaling networks to potentiating inputs, rather than relying upon the basal levels of protein phosphorylation alone, the authors were able to discern unique cancer network profiles that correlated with genetics and disease outcome. Strikingly, the authors write, individual cancers manifested multiple cell subsets with unique network profiles, reflecting cancer heterogeneity at the level of signaling response. The results show a dramatic remodeling of signaling networks in cancer cells. Thus, single cell measurements of phospho-protein responses reveal shifts in signaling potential of a phospho-protein network, allowing for categorizing of cell network phenotypes by multidimensional molecular profiles of signaling, they conclude.

Emanuel Petricoin

Co-Director, FDA/NIH Proteomics Initiative

Large-scale characterization of HeLa cell nuclear phosphoproteins

Beausoleil S, Jedrychowski M, Schwartz D, Elias J, Villén J, Li J, Cohn M, Cantley, L, Gygi S. PNAS. 2004; 101: 12130-12135.

Steven Gygi and his colleagues at Harvard Medical School describe in this paper in PNAS how they applied strong cation exchange chromatography and tandem mass spectrometry to isolate and identify phosphorylation sites. Determining the site of a regulatory phosphorylation event, the authors write, is often essential for elucidating specific kinase¯substrate relationships, providing a handle for understanding essential signaling pathways and ultimately allowing insights into numerous disease pathologies. Their experimental strategy enriched phosphopeptides from the nuclear fraction of HeLa cell lysate, and then used tandem MS to identify 2,002 phosphorylation sites from 967 proteins. This unprecedented large collection of sites permitted a detailed accounting of known and unknown kinase motifs and substrates, the authors conclude. Yates says the paper is significant because it demonstrates how MS3 can be used to create a more complex ion fragmentation pattern as a means of identifying a large number of phosphorylation sites.

John Yates

Professor, Department of Cell Biology

Scripps Research Institute

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