SCID mouse thymic lymphoma transduced with Early Growth Response transcriptional regulator. Mus musculus

Gradations in ERK signaling have been implicated in essentially every developmental checkpoint or differentiation process encountered by lymphocytes. Yet, despite intensive effort, the molecular basis by which differences in ERK activation specify alternative cell fates remains poorly understood. We report here that differential ERK signaling controls lymphoid fate specification through an alternative mode of action. While ERK phosphorylates most substrates, such as Rsk, by targeting them through its D-domain, this well-studied mode of ERK action was dispensable for development of gamma-delta T cells. Instead, development of gamma-delta T cells was dependent upon an alternative mode of action mediated by the DEF-binding pocket (DBP) of ERK. This domain enabled ERK to bind a distinct and select set of proteins required for specification of the gamma-delta fate. These data provide the first in vivo demonstration for the role of DBP-mediated interactions in orchestrating alternate ERK-dependent developmental outcomes. Overall design: RNA profiles of a scid thymic lymphoma (Scid.adh) transduced with either EGR1, EGR2, EGR3, EGR4 or stimulated through a chimeric receptor, “TAC:E stimulated,” were hybed against a reference pool RNA derived from non transduced Scid.adh. This series contains one pair of samples, Scid.adh transduced with EGR1 hybed against non-transduced Scid.adh. Samples were hybed on 2-color Agilent arrays with dye swaps. There are no replicate samples. Additional data has been requested by the GEO staff in order to complete this submission. Please contact the submitter (contact details below) for additional information or to ascertain when the missing data will be uploaded to GEO.