Bryostatin 1 (bryo 1) is known to induce the differentiation and cell cycle arrest of @entity1 @entity706 cells in vitro. The @entity3963 ( @entity3963 ), originally identified as a @entity1 in mitogenic signaling, has recently been implicated in the signaling of cellular differentiation. To examine the role of the @entity3963 /mitogen-activated protein (MAP) kinase pathway in B-lymphoid cell differentiation of the Reh @entity981 cell line, the effects of bryo 1 on @entity3963 activation were determined. On bryo 1 treatment, the activity of ERK2 (p42) rapidly increased, with ERK1 (p44) protein levels remaining constant. p44/42 immunoprecipitates from lysates of bryo 1-treated cells had increased their ability to phosphorylate the transcription factor @entity2498 -1. Constitutive AP-1 activity was shown to be potentiated after bryo 1 treatment using electrophoretic mobility shift assays. The protein composition of the AP-1 transcription factor complex activated by bryo 1 was analyzed using supershift analysis with specific antibodies against @entity1639 , @entity12861 , @entity1178 , @entity1178 B, and @entity1178 D proteins. Supershift analysis revealed that the bryo 1-induced AP-1 complex was composed predominantly of @entity1639 B and @entity1178 D. Therefore, we evaluated the effects of inhibiting @entity8047 ( @entity8047 ) on both DNA binding and cellular differentiation. Treatment of Reh cells with 20 microM @entity4286 , a specific inhibitor of @entity8047 , inhibited bryo 1-induced @entity3963 activity and DNA binding. Furthermore, @entity4286 blocked the bryo 1-induced differentiation of Reh cells, as assessed by a number of features associated with lymphoid differentiation, including changes in morphology, cell growth arrest, attachment, and increased expression of the leukocyte integrin @entity2935 . Moreover, transient transfection of Reh cells with antisense MAP kinase oligonucleotides blocked bryo 1-induced expression of @entity2935 . Our analysis also shows that @entity2935 's gene promoter activity is augmented by bryo 1. Therefore, we conclude that activation of the @entity8047 / @entity3963 signaling pathway is necessary for bryo 1-induced differentiation of the pre-B @entity981 cell line Reh.

Mitogen-activated protein kinase is required for bryostatin 1-induced differentiation of the XXXX @entity981 cell line Reh.

@entity1 :: ('9606', 'Species') :: ['human', 'participant'] @entity981 :: ('MESH:D054198', 'Disease') :: ['Acute Lymphoblastic Leukemia'] @entity8047 :: ('5609', 'Gene') :: ['MAP/ERK kinase', 'MEK'] @entity12861 :: ('2354', 'Gene') :: ['Fos B'] @entity706 :: ('MESH:D008223', 'Disease') :: ['lymphoid leukemia'] @entity3963 :: ('5594', 'Gene') :: ['extracellular signal-regulated kinase', 'ERK'] @entity1639 :: ('2353', 'Gene') :: ['Fos', 'c-Fos'] @entity1178 :: ('3725', 'Gene') :: ['Jun', 'c-Jun'] @entity2498 :: ('9860', 'Species') :: ['Elk'] @entity4286 :: ('MESH:C093973', 'Chemical') :: ['PD98059'] @entity2935 :: ('3687', 'Gene') :: ['CD11c']
@entity1 :: (9606,Species) :: ['human']
