The linker between SH2 and kinase domains positively regulates catalysis of the Tec family kinases.

Abstract:

:Tec family nonreceptor tyrosine kinases are key immunological enzymes that control processes that range from T and B cell development to reorganization of the actin cytoskeleton. The full-length Tec kinases have been resistant to crystallization. This lack of structural data and the paucity of in vitro biochemical data for this kinase family leave a void in our understanding of Tec kinase regulation. In this report we have used interleukin-2 tyrosine kinase (Itk) as a model system to gain insight into the regulatory apparatus of the Tec kinases. Use of a quantitative in vitro kinase assay has uncovered an essential role for the short linker region flanked by the SH2 and kinase domains of Itk in positively regulating Itk catalytic activity. The precise residues that allosterically regulate Itk are conserved among Tec kinases, pointing to the conserved nature of this regulatory mechanism within the family. These findings indicate that Tec kinases are not regulated in the same manner as the Src kinases but rather share some of the regulatory features of Csk instead.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Joseph RE,Min L,Andreotti AH

doi

10.1021/bi602512e

subject

Has Abstract

pub_date

2007-05-08 00:00:00

pages

5455-62

issue

18

eissn

0006-2960

issn

1520-4995

journal_volume

46

pub_type

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