PMID- 10400611 OWN - NLM STAT- MEDLINE DCOM- 19990819 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 274 IP - 29 DP - 1999 Jul 16 TI - Activation of the lck tyrosine-protein kinase by the binding of the tip protein of herpesvirus saimiri in the absence of regulatory tyrosine phosphorylation. PG - 20056-9 AB - The Tip protein of herpesvirus saimiri 484 binds to the Lck tyrosine-protein kinase at two sites and activates it dramatically. Lck has been shown previously to be activated by either phosphorylation of Tyr394 or dephosphorylation of Tyr505. We examined here whether a change in the phosphorylation of either site was required for the activation of Lck by Tip. Remarkably, mutation of both regulatory sites of tyrosine phosphorylation did not prevent activation of Lck by Tip either in vivo or in a cell free in vitro system. Tip therefore appears to be able to activate Lck through an induced conformational change that does not necessarily involve altered phosphorylation of the kinase. Tip may represent the prototype of a novel type of regulator of tyrosine-protein kinases. FAU - Hartley, D A AU - Hartley DA AD - Molecular Biology and Virology Laboratory, The Salk Institute, La Jolla, California 92037, USA. FAU - Hurley, T R AU - Hurley TR FAU - Hardwick, J S AU - Hardwick JS FAU - Lund, T C AU - Lund TC FAU - Medveczky, P G AU - Medveczky PG FAU - Sefton, B M AU - Sefton BM LA - eng GR - CA14195/CA/NCI NIH HHS/United States GR - CA42350/CA/NCI NIH HHS/United States GR - CA42364/CA/NCI NIH HHS/United States GR - etc. PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Phosphoproteins) RN - 0 (Viral Proteins) RN - 0 (tyrosine kinase interacting protein, Saimiriine herpesvirus 2) RN - EC 2.7.10.2 (Lymphocyte Specific Protein Tyrosine Kinase p56(lck)) SB - IM MH - Cell Line MH - Enzyme Activation MH - Herpesvirus 2, Saimiriine/*metabolism MH - Humans MH - Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/*metabolism MH - Mutagenesis MH - Phosphoproteins/*metabolism MH - Phosphorylation MH - Protein Binding MH - Viral Proteins/*metabolism EDAT- 1999/07/10 00:00 MHDA- 1999/07/10 00:01 CRDT- 1999/07/10 00:00 PHST- 1999/07/10 00:00 [pubmed] PHST- 1999/07/10 00:01 [medline] PHST- 1999/07/10 00:00 [entrez] AID - 10.1074/jbc.274.29.20056 [doi] AID - S0021-9258(19)72612-X [pii] PST - ppublish SO - J Biol Chem. 1999 Jul 16;274(29):20056-9. doi: 10.1074/jbc.274.29.20056.