Intrathymic signals in thymocytes are mediated by p38 mitogen-activated protein kinase.
Thymocytes develop into mature functional T cells in the inductive environment of the thymus where thymocyte-stromal cell interactions and cytokines provide survival and differentiation signals as cues for thymocyte maturation. Disruption of the thymic microenvironment results in attenuation of T cell maturation, suggesting that intrathymic signals are essential for differentiation and repertoire selection. We have previously shown that several inducible nuclear factors such as AP-1, NF-AT, and NF-kappaB are activated in response to intrathymic signals. Here we demonstrate that in thymocytes p38 mitogen-activated protein (MAP) kinase, a member of the MAP kinase family of proteins that include the extracellular-signal regulated kinases and Jun aminoterminal kinases, is highly activated in response to intrathymic signals in vivo. These studies suggest a role for p38 MAP kinase in T cell survival and differentiation.
Sen
J
J
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Kapeller
R
R
Fragoso
R
R
Sen
R
R
Zon
L I
LI
Burakoff
S J
SJ
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002454:Cell Differentiation; D015536:Down-Regulation; D004789:Enzyme Activation; D007375:Interleukin-1 / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D013601:T-Lymphocytes / Q000166:cytology* / Q000201:enzymology; D013950:Thymus Gland / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D017871:Calcium-Calmodulin-Dependent Protein Kinases