COMPLETE NUCLEOTIDE-SEQUENCE, EXPRESSION, AND CHROMOSOMAL LOCALIZATION OF HUMAN MIXED-LINEAGE KINASE-2
- Author(s)
- Dorow, DS; Devereux, L; Tu, GF; PRICE, G; Nicholl, JK; Sutherland, GR; Simpson, RJ;
- Details
- Publication Year 1995-12-01,Volume 234,Issue #2,Page 492-500
- Journal Title
- EUROPEAN JOURNAL OF BIOCHEMISTRY
- Publication Type
- Journal Article
- 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. Bioch. 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-ncid 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 pl 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.
- Publisher
- SPRINGER VERLAG
- Keywords
- RECEPTOR TYROSINE KINASES; POLYMERASE CHAIN-REACTION; LIGAND-BINDING SITE; SH3 DOMAINS; PROTEIN-KINASE; LEUCINE ZIPPER; CRYSTAL-STRUCTURE; FAMILY; IDENTIFICATION; PHOSPHORYLATION
- Publisher's Version
- https://doi.org/10.1111/j.1432-1033.1995.492_b.x
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1995-12-01 12:00:00