Where is kinase found

Phylogram of the human protein tyrosine kinase family inferred from amino acid sequences of the kinase domains. The tree is constructed by the N-J method Saitou and Nei, and the evolutionary distance is calculated by Tamura-Nei algorithm Tamura and Nei, Numbers on each node indicate the evolutionary distance. The tree is drawn to scale and is midpoint-rooted. Domain structures of the human non-receptor tyrosine kinases a and receptor tyrosine kinases b.

Data were obtained by searching the amino acid sequences of the human tyrosine kinases against the latest version 5. Domains sharing significant homologies to the Pfam-A alignments are used in this study. The schematics are shown to scale. The clustering of tyrosine kinase genes into families based on kinase domain sequence also parallels the overall domain structure of the proteins.

A diagram of the overall protein domain structure of a representative member of each tyrosine kinase family is shown in Figure 3a,b. The human tyrosine kinase families exhibit a wide spectrum of protein domains consistent with the numerous and varied interactions and functions of these molecules as reviewed by the publications in Table 1. The domain representations are not complete. Many families encode proteins for which some domains are not defined, given the current state of knowledge.

The assignment of vertebrate orthologs to the human tyrosine kinase genes was done by reciprocal BLAST searches between the human, mouse, rat, and chicken sets of tyrosine kinase genes. Pairs with reciprocal best scores were assigned as orthologs and the results are shown in Table 3a and b Walchi et al. The per cent identity and similarity for the protein kinase domains of the mouse and human orthologs are shown in the fourth column.

Cluster numbers for the murine Unigene EST database are given. Accession numbers for identified rat and chicken orthologs complete the tables. A nearly complete correspondence between the tyrosine kinase families of man and mouse exists.

There are only three human PTKs for which an orthologous murine sequence has not been discovered, and this gap is likely to be filled quickly.

Conversely, there are no identified rodent tyrosine kinases for which a human ortholog does not exist. For the non-mammalian vertebrates, such as chicken, a limited number of tyrosine kinases may not have human orthologs, as discussed previously.

This correspondence between the tyrosine kinase gene families of humans and mice reinforces the validity of mouse models for human diseases, especially cancer. The application of the human genomic sequence information should greatly aid the study of protein tyrosine kinases. As a first step, the catalog of tyrosine kinase genes in the human genome should provide a foundation for further discovery of kinase involvement in disease progression and functional characterizations.

The fact that the range of human protein tyrosine kinases was nearly identified prior to the genomic sequence information is a testament to the interest shown and quality of work performed by the numerous researchers devoted to protein kinases. Other less well-studied gene families are likely to have more surprises in the human genome.

Continuing studies on expression patterns, functional characterizations, and disease associations of tyrosine kinases, as well as studies of genetic variations at tyrosine kinase loci, should provide a basis for the development of new therapeutics for the treatment of human disease. Cell Res. Barbacid M. NY Acad. Baserga R. Birchmeier C and Gherardi E. Bruckner K and Klein R.

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Published : 20 November Issue Date : 20 November Of the 3 substrates identified previously, P and P were partly heat-stable. Thirty-one new PKG substrates were found: 14 in the initial heat-stable extract and 9 in the heat- and acid-soluble extract, whereas the others were revealed only after chromatography. After sequential application to Q-Sepharose and S-Sepharose columns, 7 PKG substrates were found in pool I, in particular a group of 4 substrates of 40, 33, 28 and 22 kD virtually coeluted through all 3 columns.

The former 3 produced similar phosphopeptide maps, suggesting a relationship. Further chromatography of the proteins in pool II resulted in an extensive purification of P as well as a group of 4 PKG substrates of kD.