The golli-myelin basic protein negatively regulates signal transduction in T lymphocytes.
Protein kinase C (PKC) plays a critical role in signal transduction controlling T lymphocyte activation. Both positive and negative regulation of signal transduction is needed for proper control of T lymphocyte activation. We have found that a golli product of the myelin basic protein (MBP) gene can serve as a negative regulator of signaling pathways in the T lymphocyte, particularly the PKC pathway. Increased expression of golli BG21 in Jurkat T cells strongly inhibits anti-CD3-induced IL-2-luciferase activity, an indicator of T lymphocyte activation. Golli BG21 can be phosphorylated by PKC in vitro and its phosphorylation increases in PMA-activated Jurkat cells. BG21 inhibits the PMA-induced increase in AP-1 or NF-kappaB activation, consistent with golli acting in a PKC-mediated cellular event. Golli BG21 inhibition of the PKC pathway is not due to a direct action on PKC activation but in the cascade following PKC activation, since BG21 neither reduces PKC enzyme activity nor blocks the membrane association of PKCtheta brought on by T lymphocyte activation. The inhibitory function of BG21 is independent of its phosphorylation by PKC because a mutant BG21, in which the PKC sites have been mutated, is as effective as the wild type BG21 in inhibiting the PMA-induced AP-1 activation. Structure-function assays indicate that BG21 inhibitory activity resides in the golli domain rather than in MBP domain of the molecule. These results reveal a novel role for MBP gene products in T lymphocytes within the immune system.
Feng
Ji-Ming
JM
UCLA Medical School, Neuropsychiatric Institute, Room 47-448, 760 Westwood Plaza, Los Angeles, CA 90024-17519, USA. jfeng@mednet.ucla.edu
Fernandes
Augustine O
AO
Campagnoni
Celia W
CW
Hu
Yan-Hong
YH
Campagnoni
Anthony T
AT
D000595:Amino Acid Sequence; D015153:Blotting, Western; D005434:Flow Cytometry; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology*; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000235:genetics / Q000276:immunology*; D009419:Nerve Tissue Proteins / Q000276:immunology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014157:Transcription Factors / Q000276:immunology*; D014162:Transfection
D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors; D011493:Protein Kinase C