PMID- 10602006 OWN - NLM STAT- MEDLINE DCOM- 20000104 LR - 20180420 IS - 0014-2980 (Print) IS - 0014-2980 (Linking) VI - 29 IP - 12 DP - 1999 Dec TI - CD8(+) T cell cytolytic activity independent of mitogen-activated protein kinase / extracellular regulatory kinase signaling (MAP kinase / ERK). PG - 3971-7 AB - Cytotoxicity is a major effector function of CD8(+) T cells. Although mitogen-activated protein kinase (MAP kinase) / extracellular regulatory kinase (ERK) activity is indispensable for cytotoxic activity of most CD8(+) T cells a portion of CD8(+) T cells appears resistant to MEK inhibition as cytotoxicity of bulk cultures was partially preserved in the presence of a MEK inhibitor. We have also identified a long-term CD8(+) T cell line with unaltered cytolytic activity after prevention of ERK activation. Antigen-induced microtubule organizing center (MTOC) reorientation was not prevented in this CD8(+) cell line by MEK inhibition, in sharp contrast to the MTOC reorientation prevention in a CD8(+) T cell clone with MEK inhibition-sensitive cytolytic activity. These findings suggest that resistance of lysis to MEK inhibition may be due to a lack of ERK control over MTOC reorientation in some CD8(+) T cells. Thus, there appears to be a heterogeneity of ERK-regulated cytolytic activity in CD8(+) T cells, most likely resulting from a differential control of ERK over MTOC motility. FAU - Lilic, M AU - Lilic M AD - Michael Heidelberger Division of Immunology Department of Pathology and Kaplan Comprehensive Cancer Center, NYU Medical Center, New York, USA. FAU - Kulig, K AU - Kulig K FAU - Messaoudi, I AU - Messaoudi I FAU - Remus, K AU - Remus K FAU - Jankovic, M AU - Jankovic M FAU - Nikolic-Zugic, J AU - Nikolic-Zugic J FAU - Vukmanovic, S AU - Vukmanovic S LA - eng GR - AI041573/AI/NIAID NIH HHS/United States GR - CA-02853/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - Germany TA - Eur J Immunol JT - European journal of immunology JID - 1273201 RN - 0 (CD8 Antigens) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - CD8 Antigens/immunology MH - CD8-Positive T-Lymphocytes/*immunology MH - *Cytotoxicity, Immunologic MH - MAP Kinase Signaling System/*immunology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mitogen-Activated Protein Kinases/*immunology MH - Signal Transduction/*immunology EDAT- 1999/12/22 00:00 MHDA- 1999/12/22 00:01 CRDT- 1999/12/22 00:00 PHST- 1999/12/22 00:00 [pubmed] PHST- 1999/12/22 00:01 [medline] PHST- 1999/12/22 00:00 [entrez] AID - 10.1002/(SICI)1521-4141(199912)29:12<3971::AID-IMMU3971>3.0.CO;2-5 [doi] PST - ppublish SO - Eur J Immunol. 1999 Dec;29(12):3971-7. doi: 10.1002/(SICI)1521-4141(199912)29:12<3971::AID-IMMU3971>3.0.CO;2-5.