Regulation of Lck activity by the Herpes virus saimiri Tip484 and Tip488 proteins

Peter Kjellen

Appointment Period: 2000-2001 / Grant Year: [16]

I have been investigating the regulation of Lck by the Herpesvirus saimiri Tip484 and Tip488 proteins. Strains of Herpesvirus saimiri of the subgroup C efficiently induce leukemia in New World primates and transform human lymphocytes. The tyrosine kinase interacting protein, Tip, which is only expressed by Herpesvirus saimiri of subgroup C, is essential for transformation. The binding of the viral Tip protein to Lck, a member of the Src-family of tyrosine protein kinases, is likely to be important for T cell transformation by Herpesvirus saimiri. Understanding how Tip modulates Lck activity is therefore important for elucidating the mechanism of Herpesvirus saimiri leukemogenesis. Our data suggest that Herpesvirus saimiri infection increases the activity of Lck through the action of Tip and that this activation plays a role in T cell leukemogenesis.

PUBLICATIONS (resulting from this training, and some recent ones)

Kjellen P, Amdjadi K, Lund TC, Medveczky PG, Sefton BM. (2002) The herpesvirus saimiri tip484 and tip488 proteins both stimulate lck tyrosine protein kinase activity in vivo and in vitro. Virology. 297:281-8.

Lindqvist AK, Nakken B, Sundler M, Kjellen P, Jonsson R, Holmdahl R, Skarstein K. (2005) Influence on spontaneous tissue inflammation by the major histocompatibility complex region in the nonobese diabetic mouse. Scand J Immunol. 61:119-27.

Holm L, Kjellen P, Holmdahl R, Kihlberg J. (2005) Identification of the minimal glycopeptide core recognized by T cells in a model for rheumatoid arthritis. Bioorg Med Chem. 13:473-82.

Weis DD, Kjellen P, Sefton BM, Engen JR. (2006) Altered dynamics in Lck SH3 upon binding to the LBD1 domain of Herpesvirus saimiri Tip. Protein Sci. 15:2402-10.