Application of Active and Kinase-Deficient Kinome Collection for Identification of Kinases Regulating Hedgehog Signaling

@article{citeulike:2758434, abstract = {Summary To allow genome-scale identification of genes that regulate cellular signaling, we cloned >90\% of all human full-length protein kinase cDNAs and constructed the corresponding kinase activity-deficient mutants. To establish the utility of this resource, we tested the effect of expression of the kinases on three different cellular signaling models. In all screens, many kinases had a modest but significant effect, apparently due to crosstalk between signaling pathways. However, the strongest effects were found with known regulators and novel components, such as MAP3K10 and DYRK2, which we identified in a mammalian Hedgehog (Hh) signaling screen. DYRK2 directly phosphorylated and induced the proteasome-dependent degradation of the key Hh pathway-regulated transcription factor, GLI2. MAP3K10, in turn, affected GLI2 indirectly by modulating the activity of DYRK2 and the known Hh pathway component, GSK3[beta]. Our results establish kinome expression screening as a highly effective way to identify physiological signaling pathway components and genes involved in pathological signaling crosstalk.}, author = {Varjosalo, Markku and Bj\"{o}rklund, Mikael and Cheng, Fang and Syv\"{a}nen, Heidi and Kivioja, Teemu and Kilpinen, Sami and Sun, Zairen and Kallioniemi, Olli and Stunnenberg, Hendrik G. and He, Wei-Wu and Ojala, P\"{a}ivi and Taipale, Jussi }, citeulike-article-id = {2758434}, doi = {10.1016/j.cell.2008.02.047}, journal = {Cell}, month = {May}, number = {3}, pages = {537--548}, posted-at = {2008-05-07 09:51:21}, priority = {2}, title = {Application of Active and Kinase-Deficient Kinome Collection for Identification of Kinases Regulating Hedgehog Signaling}, url = {http://dx.doi.org/10.1016/j.cell.2008.02.047}, volume = {133}, year = {2008} }

TY - JOUR ID - citeulike:2758434 L3 - citeulike-article-id:2758434 TI - Application of Active and Kinase-Deficient Kinome Collection for Identification of Kinases Regulating Hedgehog Signaling JF - Cell VL - 133 IS - 3 SP - 537 EP - 548 N2 - Summary To allow genome-scale identification of genes that regulate cellular signaling, we cloned >90% of all human full-length protein kinase cDNAs and constructed the corresponding kinase activity-deficient mutants. To establish the utility of this resource, we tested the effect of expression of the kinases on three different cellular signaling models. In all screens, many kinases had a modest but significant effect, apparently due to crosstalk between signaling pathways. However, the strongest effects were found with known regulators and novel components, such as MAP3K10 and DYRK2, which we identified in a mammalian Hedgehog (Hh) signaling screen. DYRK2 directly phosphorylated and induced the proteasome-dependent degradation of the key Hh pathway-regulated transcription factor, GLI2. MAP3K10, in turn, affected GLI2 indirectly by modulating the activity of DYRK2 and the known Hh pathway component, GSK3[beta]. Our results establish kinome expression screening as a highly effective way to identify physiological signaling pathway components and genes involved in pathological signaling crosstalk. AU - Varjosalo, Markku AU - Björklund, Mikael AU - Cheng, Fang AU - Syvänen, Heidi AU - Kivioja, Teemu AU - Kilpinen, Sami AU - Sun, Zairen AU - Kallioniemi, Olli AU - Stunnenberg, Hendrik AU - He, Wei-Wu AU - Ojala, Päivi AU - Taipale, Jussi PY - 2008/05/02/ UR - http://dx.doi.org/10.1016/j.cell.2008.02.047 ER -