Tyrosine kinase specific motif at subdomain VIII does not confer specificity for tyrosine

The majority of protein kinases fall within one of the two broad classes, kinases that phosphorylate serine or threonine and kinases that phosphorylate tyrosine. The structural basis that confers residue specificity is not known. However, it has been hypothesized that a region in subdomain VIII of the catalytic domain may be involved in determining kinase specificity. This region contains a motif which is conserved among serine/threonine kinases and different from the one conserved among tyrosine kinases. We have prepared a chimera of the tyrosine kinase pp56lck in which the tyrosine kinase motif at subdomain VIII has been exchanged for the corresponding region of the serine/threonine kinase c-Raf. Our results indicate that this motif itself does not confer amino acid specificity since the chimeric kinase still displays specificity for tyrosine.