LOK Is a Novel Mouse STE20-like Protein Kinase That Is Expressed Predominantly in Lymphocytes*
- Satomi Kuramochi‡,
- Tetsuo Moriguchi§,
- Keisuke Kuida‡,
- Junji Endo‡,
- Kentaro Semba¶,
- Eisuke Nishida§ and
- Hajime Karasuyama‡‖
- From the ‡Department of Immunology, The Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113, the§Department of Biophysics, Faculty of Science, Kyoto University, Sakyo-ku, Kyoto 606-01, and the ¶Department of Cellular and Molecular Biology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108, Japan
Abstract
We have identified a new gene, designatedlok (lymphocyte-oriented kinase), that encodes a 966-amino acid protein kinase whose catalytic domain at the N terminus shows homology to that of the STE20 family members involved in mitogen-activated protein (MAP) kinase cascades. The non-catalytic domain of LOK does not have any similarity to that of other known members of the family. There is a proline-rich motif with Src homology region 3 binding potential, followed by a long coiled-coil structure at the C terminus. LOK is expressed as a 130-kDa protein, which was detected predominantly in lymphoid organs such as spleen, thymus, and bone marrow, in contrast to other mammalian members of the STE20 family. LOK phosphorylated itself as well as substrates such as myelin basic protein and histone IIA on serine and threonine residues but not on tyrosine residues, establishing LOK as a novel serine/threonine kinase. When coexpressed in COS7 cells with the known MAP kinase isoforms (ERK, JNK, and p38), LOK activated none of them in contrast to PAK- and GCK-related kinases. These results suggest that LOK could be involved in a novel signaling pathway in lymphocytes, which is distinct from the known MAP kinase cascades.
Footnotes
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↵* This work was supported in part by grants-in-aid from the Ministry of Education, Science and Culture, Japan, the Uehara Memorial Foundation, and the Mochida Memorial Foundation for Medical and Pharmaceutical Research.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) D89728.
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↵‖ To whom correspondence should be addressed. Tel.: 81-3-3823-2101 (ext. 5218); Fax: 81-3-5685-6608; E-mail:karasuyama{at}rinshoken.or.jp.
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↵1 The abbreviations used are: MAP, mitogen-activated protein; MAPKK, MAP kinase kinase; MAPKKK, MAP kinase kinase kinase; RT, reverse transcription; PCR, polymerase chain reaction; MKK, MAP kinase kinase; GST, glutathioneS-transferase; SH, Src homology; MBP, myelin basic protein; PAK, p21-activated kinase.
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↵2 S. Kuramochi and H. Karasuyama, unpublished observation.
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- Received May 27, 1997.
