LCK UNIQUE DOMAIN INFLUENCES LCK SPECIFICITY AND BIOLOGICAL FUNCTION

Citation
Ac. Carrera et al., LCK UNIQUE DOMAIN INFLUENCES LCK SPECIFICITY AND BIOLOGICAL FUNCTION, The Journal of biological chemistry, 270(7), 1995, pp. 3385-3391
Citations number
45
Categorie Soggetti
Biology
ISSN journal
00219258
Volume
270
Issue
7
Year of publication
1995
Pages
3385 - 3391
Database
ISI
SICI code
0021-9258(1995)270:7<3385:LUDILS>2.0.ZU;2-1
Abstract
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.