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Biochemistry, Biophysics, and Structural Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

Molecular Biology

2009

Series

Btk

Articles 1 - 2 of 2

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Sh2-Dependent Autophosphorylation Within The Tec Family Kinase Itk, Raji E. Joseph, Andrew Severin, Lie Min, D. Bruce Fulton, Amy H. Andreotti Aug 2009

Sh2-Dependent Autophosphorylation Within The Tec Family Kinase Itk, Raji E. Joseph, Andrew Severin, Lie Min, D. Bruce Fulton, Amy H. Andreotti

Biochemistry, Biophysics and Molecular Biology Publications

The Tec family kinase, Itk (interleukin-2 tyrosine kinase), undergoes an in cis autophosphorylation on Y180 within its Src homology 3 (SH3) domain. Autophosphorylation of the Itk SH3 domain by the Itk kinase domain is strictly dependent on the presence of the intervening Src homology 2 (SH2) domain. A direct docking interaction between the Itk kinase and SH2 domains brings the Itk SH3 domain into the active site where Y180 is then phosphorylated. We now identify the residues on the surface of the Itk SH2 domain responsible for substrate docking and show that this SH2 surface mediates autophosphorylation in the full-length ...


Conformational Snapshots Of Tec Kinases During Signaling, Raji E. Joseph, Amy H. Andreotti Mar 2009

Conformational Snapshots Of Tec Kinases During Signaling, Raji E. Joseph, Amy H. Andreotti

Biochemistry, Biophysics and Molecular Biology Publications

The control of cellular signaling cascades is of utmost importance in regulating the immune response. Exquisitely precise protein-protein interactions and chemical modification of substrates by enzymatic catalysis are the fundamental components of the signals that alert immune cells to the presence of a foreign antigen. In particular, the phosphorylation events induced by protein kinase activity must be spatially and temporally regulated by specific interactions to maintain a normal and effective immune response. High resolution structures of many protein kinases along with supporting biochemical data are providing significant insight into the intricate regulatory mechanisms responsible for controlling cellular signaling. The Tec ...