Abstract
A protein called Tip (tyrosine kinase interacting protein) of herpesvirus saimiri associates with Lck in virus-transformed human T cells and is an in vitro substrate for Lck kinase. Mutational analyses of a GST-Tip fusion protein revealed that binding to Lck requires putative SH3 binding sequences and a sequence homologous to the carboxyl terminus of Src-related kinases. These sequences are referred to as SH3-Binding (SH3B) and C-terminal Src-related Kinase Homology (CSKH) elements. Peptide fragments as short as 37 amino acids containing both SH3B and CSKH elements were sufficient to form a stable complex with Lck in vitro. Furthermore, these same sequences of Tip were necessary for in vivo association with Lck when Tip and Lck were expressed transiently in COS-1 cells or stably in Rat-1 cell lines. These results demonstrate that the CSKH element of Tip participates in the binding of sequences within Lck. Tip of herpesvirus saimiri has apparently acquired such CSKH and SH3B elements for the purpose of targeting cellular protein kinases. The interaction of Tip with Lck may influence Lck kinase activity or its binding to other cellular proteins and thereby alter Lck function in T cells infected by h. saimiri.
Highlights
THE JOURNAL OF BIOLOGICAL CHEMISTRYVol 270, No 35, Issue of September 1, pp. 20660-20667, 1995 Printed in U.S.A. Jae U
A protein called tyrosine kinase interacting protein (Tip) (!yrosine kinase interacting protein) ofherpesvirus saimiri associates with Lck in vtrustransformed human T cells and is an in vitro substrate for Lck kinase
These results demonstrate that the C-terminal Src-related Kinase Homology (CSKH) element of Tip participates in the binding of sequences within Lck
Summary
Vol 270, No 35, Issue of September 1, pp. 20660-20667, 1995 Printed in U.S.A. Jae U. Cells or stably in Rat-I cell lines These results demonstrate that the CSKH element of Tip participates in the binding of sequences within Lck. Tip of herpesvirus saimiri has apparently acquired such CSKH and SH3B elements for the purpose of targeting cellular protein kinases. Nucleotide sequence analysis of the entire HVS genome revealed a number of genes with homology to cellular proteins, some of which are likely to contribute to T cell transformation [14]. Lck and phosphorylated on tyrosine residues by purified Lck in several cell-free assay systems [21] It was designated as tyrosine kinase interacting protein (Tip) [21]. These two structural elements are a proline-rich segment similar to sequences known to bind to SH3 domains and a motif homologous to the carboxyl-terminal regulatory region of Src-related tyrosine kinases.
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