Buchmann Institut für Molekulare Lebenswissenschaften (BMLS)
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The Kinase Chemogenomic Set (KCGS): An open science resource for kinase vulnerability identification
(2019)
We describe the assembly and annotation of a chemogenomic set of protein kinase inhibitors as an open science resource for studying kinase biology. The set only includes inhibitors that show potent kinase inhibition and a narrow spectrum of activity when screened across a large panel of kinase biochemical assays. Currently, the set contains 187 inhibitors that cover 215 human kinases. The kinase chemogenomic set (KCGS) is the most highly annotated set of selective kinase inhibitors available to researchers for use in cell-based screens.
Formation of the anteroposterior and dorsoventral body axis in the Caenorhabditis elegans embryo depends on cortical actomyosin flows and advection of polarity determinants. The role of this patterning mechanism in tissue polarization immediately after formation of cell-cell contacts is not fully understood. Here, we demonstrate that planar cell polarity (PCP) is established in the C. elegans embryo at the time of left-right (l/r) symmetry breaking. At this stage, centripetal cortical flows asymmetrically and differentially advect anterior polarity determinants (aPARs) PAR-3, PAR-6 and PKC-3 from cell-cell contacts to the medial cortex, which results in their unmixing from apical myosin. Advection generally requires GSK-3 and CDC-42, while advection of PAR-6 specifically depends on the RhoGAP PAC-1. Concurrent asymmetric retention of PAR-3, E-cadherin/HMR-1, PAC-1 and opposing retention of the antagonistic Wnt pathway components APC/APR-1 and Frizzled/MOM-5 at apical cell-cell contacts leads to planar asymmetries. The most obvious mark of PCP, asymmetric retention of PAR-3 at posterior cell-cell contacts on the left side of the embryo, is required for proper cytokinetic cell intercalation. Hence, our data uncover how PCP can be established through Wnt signaling as well as dissociation and planar asymmetric retention of aPARs mediated by distinct Rho GTPases and their regulators.