Ac. Carrera et al., LCK UNIQUE DOMAIN INFLUENCES LCK SPECIFICITY AND BIOLOGICAL FUNCTION, The Journal of biological chemistry, 270(7), 1995, pp. 3385-3391
Src-family tyrosine kinases share structural and amino acid sequence h
omology, particularly in the catalytic domain as well as in the SH2 an
d SH3 domains of the regulatory region. However, each src-family membe
r also contains a unique domain which is specific to and characteristi
c of each individual tyrosine kinase. These unique or specific domains
may contribute to the functional specificity of each src-family kinas
e. To address this possibility, we analyzed the kinase activities and
substrate specificities of the lymphoid src-kinase, pp56(lck), and a m
utant of pp56(lck) lacking its specific domain. Our data show that bot
h the wild type enzyme and the specific domain-deleted mutant displaye
d similar affinities for ATP and the non-physiological substrate denat
ured enolase. However, the specific domain-deleted mutant failed to ph
osphorylate a number of physiological substrates of pp56(lck). In addi
tion, the ability of pp56(lck) to mediate induction of the interleukin
-2 promoter was strongly impaired upon deletion of its specific domain
. Thus, the unique domain is not required for the intrinsic kinase act
ivity of pp56(lck), however, it influences substrate preference and co
ntributes to the unique physiological function of this src-family tyro
sine kinase.