Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/7214
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Type: Journal article
Title: Complete nucleotide sequence, expression and chromosomal localization of human mixed-lineage kinase 2
Author: Dorow, D.
Devereaux, L.
Tu, G.F.
Price, G.
Nicholl, J.
Sutherland, G.
Simpson, R.
Citation: The Federation of European Biochemical Societies (FEBS) Journal, 1995; 234(2):492-500
Publisher: Federation of European Biochemical Societies
Issue Date: 1995
ISSN: 0014-2956
1432-1033
Statement of
Responsibility: 
Donna S. Dorow, Lisa Devereux, Guo-fen Tu, Gareth Price, Jillian K. Nicholl, Grant R. Sutherland and Richard J. Simpson
Abstract: Protein kinases play pivotal roles in the control of many cellular processes. In a search for protein kinases expressed in human epithelial tumour cells, we discovered two members of a novel protein kinase family [Dorow, D. S., Devereux, L., Dietzsch, E. & de Kretser, T. A. (1993) Eur. J. Biochem. 213, 701-710]. Due to the unique mixture of structural domains within their amino acid sequences, we named the family mixed-lineage kinases (MLK). We initially isolated clones encoding partial cDNAs of MLK1 and 2 from a human colonic cDNA library. The MLK2 cDNA was subsequently used to screen a human brain cDNA library and we have now cloned and sequenced a 3454-bp cDNA encoding the full-length MLK2 protein. The predicted MLK2 polypeptide has 954 amino acids and contains a src homology 3 (SH3) domain, a kinase catalytic domain, a double leucine zipper and basic domain, and a large C-terminal domain. The 22-amino-acid N-terminal region has four glutamic acid residues immediately following the initiator methionine. Beginning at amino acid 23, the 55-amino-acid SH3 domain contains a 5-amino-acid insert in a position corresponding to inserts of 6 and 15 residues in the SH3 domains of n-src and the phosphatidylinositol 3'-kinase. Adjacent to the SH3 domain is a kinase catalytic domain with conserved motifs associated with both serine/threonine and tyrosine specificity. Beginning nine residues C-terminal to the catalytic domain, there are two leucine/isoleucine zippers separated by a 13-amino-acid spacer sequence and followed by a stretch of basic residues. The polybasic sequence contains a motif that is similar to nuclear localisation signals from several proteins. The C-terminal domain is composed of 491 amino acids of which 17% are serine or threonine and 16% are proline. This domain also has a biased ratio of basic to acidic amino acids with a calculated pI of 9.38. When used as a probe to examine mRNA expression in human tissues, a MLK2 cDNA hybridised to a species of 3.8 kb that was expressed at highest levels in RNA from brain and skeletal muscle. The 3454-bp cDNA was also used for fluorescence in situ hybridisation to localise the MLK2 gene to human chromosome 19 q13.2.
Keywords: protein kinase
mixed-lineage kinase
leucine zipper
SH3 domain
DNA sequence
DOI: 10.1111/j.1432-1033.1995.492_b.x
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Paediatrics publications

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