Lack of Csk-mediated negative regulation in a unicellular Src kinase
PMCID: PMC3567254
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American Chemical Society
2012-09-21
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| Online Access: | http://hdl.handle.net/10261/113450 http://dx.doi.org/10.13039/100000002 http://dx.doi.org/10.13039/501100000781 http://dx.doi.org/10.13039/501100004837 |
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dig-ibe-es-10261-1134502021-12-28T16:23:48Z Lack of Csk-mediated negative regulation in a unicellular Src kinase Schultheiss, Kira P. Suga, Hiroshi Ruiz-Trillo, Iñaki Miller, W. Todd National Institutes of Health (US) European Research Council Ministerio de Ciencia e Innovación (España) PMCID: PMC3567254 Phosphotyrosine-based signaling plays a vital role in cellular communication in multicellular organisms. Unexpectedly, unicellular choanoflagellates (the closest phylogenetic group to metazoans) possess numbers of tyrosine kinases that are comparable to those in complex metazoans. Here, we have characterized tyrosine kinases from the filasterean Capsaspora owczarzaki, a unicellular protist representing the sister group to choanoflagellates and metazoans. Two Src-like tyrosine kinases have been identified in C. owczarzaki (CoSrc1 and CoSrc2), both of which have the arrangement of SH3, SH2, and catalytic domains seen in mammalian Src kinases. In Capsaspora cells, CoSrc1 and CoSrc2 localize to punctate structures in filopodia that may represent primordial focal adhesions. We have cloned, expressed, and purified both enzymes. CoSrc1 and CoSrc2 are active tyrosine kinases. Mammalian Src kinases are normally regulated in a reciprocal fashion by autophosphorylation in the activation loop (which increases activity) and by Csk-mediated phosphorylation of the C-terminal tail (which inhibits activity). Similar to mammalian Src kinases, the enzymatic activities of CoSrc1 and CoSrc2 are increased by autophosphorylation in the activation loop. We have identified a Csk-like kinase (CoCsk) in the genome of C. owczarzaki. We cloned, expressed, and purified CoCsk and found that it has no measurable tyrosine kinase activity. Furthermore, CoCsk does not phosphorylate or regulate CoSrc1 or CoSrc2 in cells or in vitro, and CoSrc1 and CoSrc2 are active in Capsaspora cell lysates. Thus, the function of Csk as a negative regulator of Src family kinases appears to have arisen with the emergence of metazoans. © 2012 American Chemical Society. Work in W.T.M.’s laboratory was supported by Grant CA58530 from the National Institutes of Health. Work in I.R.-T.’s lab was supported by a European Research Council Starting Grant (ERC-2007-StG-206883) and a grant (BFU2008-02839/BMC) from Ministerio de Ciencia e Innovación (MICINN). Peer Reviewed 2015-04-09T12:30:47Z 2015-04-09T12:30:47Z 2012-09-21 2015-04-09T12:30:49Z artículo http://purl.org/coar/resource_type/c_6501 doi: 10.1021/bi300965h issn: 0006-2960 e-issn: 1520-4995 Biochemistry 51(41): 8267-8277 (2012) http://hdl.handle.net/10261/113450 10.1021/bi300965h http://dx.doi.org/10.13039/100000002 http://dx.doi.org/10.13039/501100000781 http://dx.doi.org/10.13039/501100004837 22998693 #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/EC/FP7/206883 Postprint http://dx.doi.org/10.1021/bi300965h Sí open American Chemical Society |
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PMCID: PMC3567254 |
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National Institutes of Health (US) Schultheiss, Kira P. Suga, Hiroshi Ruiz-Trillo, Iñaki Miller, W. Todd |
| format |
artículo |
| author |
Schultheiss, Kira P. Suga, Hiroshi Ruiz-Trillo, Iñaki Miller, W. Todd |
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Schultheiss, Kira P. Suga, Hiroshi Ruiz-Trillo, Iñaki Miller, W. Todd Lack of Csk-mediated negative regulation in a unicellular Src kinase |
| author_sort |
Schultheiss, Kira P. |
| title |
Lack of Csk-mediated negative regulation in a unicellular Src kinase |
| title_short |
Lack of Csk-mediated negative regulation in a unicellular Src kinase |
| title_full |
Lack of Csk-mediated negative regulation in a unicellular Src kinase |
| title_fullStr |
Lack of Csk-mediated negative regulation in a unicellular Src kinase |
| title_full_unstemmed |
Lack of Csk-mediated negative regulation in a unicellular Src kinase |
| title_sort |
lack of csk-mediated negative regulation in a unicellular src kinase |
| publisher |
American Chemical Society |
| publishDate |
2012-09-21 |
| url |
http://hdl.handle.net/10261/113450 http://dx.doi.org/10.13039/100000002 http://dx.doi.org/10.13039/501100000781 http://dx.doi.org/10.13039/501100004837 |
| work_keys_str_mv |
AT schultheisskirap lackofcskmediatednegativeregulationinaunicellularsrckinase AT sugahiroshi lackofcskmediatednegativeregulationinaunicellularsrckinase AT ruiztrilloinaki lackofcskmediatednegativeregulationinaunicellularsrckinase AT millerwtodd lackofcskmediatednegativeregulationinaunicellularsrckinase |
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