OBJECTIVE: The retroviral oncogene v-Cbl causes pre-B cell lymphomas and @entity2800 in @entity19 , and its @entity238 homologue is oncogenic, causing enhanced receptor @entity669 kinase signaling. The @entity1 Cbl gene resides at 11q23. The aim of this study is to determine the effect of oncogenic Cbl on growth-regulating responses. MATERIALS AND METHODS: The oncogenic mutant of Cbl (CblDelta1-357) was transfected into factor-dependent 32Dcl3 myeloid cells. Consequently, cell survival and differentiation were measured. @entity18226 , @entity10255 , MAP kinase, and @entity4357 3'(PI3')-kinase activities, protein phosphorylation, @entity588 promoter activity, ubiquitination, and levels of @entity588 , @entity589 , @entity1835 , and @entity1836 were determined. In addition, the effect of v-Cbl on TF-1 cell survival upon granulocyte-macrophage colony-stimulating factor withdrawal was studied. RESULTS: 32Dcl3 and TF-1 cells expressing v-Cbl showed resistance to apoptosis upon growth factor withdrawal, and 32Dcl3 cells completely failed to respond to @entity1261 's induction of differentiation. Basal activities of @entity18226 , @entity10255 , and PI3'-kinase were elevated in the v-Cbl line. There was neither enhanced @entity669 phosphorylation of cellular protein content, Cbl, or @entity4016 , nor @entity563 phosphorylation of MAP kinase or @entity584 . After factor withdrawal, the level of @entity588 was greater in v-Cbl cells than in control cells. CONCLUSIONS: Neither increased @entity588 promoter activity nor decreased ubiquitination of @entity588 could account for increased @entity588 levels. v-Cbl-expressing 32Dcl3 cells were resistant to differentiation. v-Cbl suppresses apoptosis and differentiation, possibly through enhancement of @entity18226 , @entity10255 , and PI3'-kinase activities and @entity588 .

Suppression of apoptosis and XXXX -induced differentiation by an oncogenic form of Cbl.

@entity1 :: ('9606', 'Species') :: ['human'] @entity18226 :: ('4067', 'Gene') :: ['Lyn'] @entity589 :: ('581', 'Gene') :: ['Bax'] @entity588 :: ('596', 'Gene') :: ['Bcl-2'] @entity1261 :: ('1440', 'Gene') :: ['granulocyte colony-stimulating factor'] @entity4357 :: ('MESH:D010716', 'Chemical') :: ['phosphatidylinositol'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity1836 :: ('598', 'Gene') :: ['Bcl-x(L)'] @entity2800 :: ('MESH:D007951', 'Disease') :: ['myeloid leukemias'] @entity4016 :: ('3717', 'Gene') :: ['Jak2'] @entity10255 :: ('6850', 'Gene') :: ['Syk'] @entity584 :: ('207', 'Gene') :: ['Akt'] @entity563 :: ('CHEBI:17822', 'Chemical') :: ['serine'] @entity669 :: ('CHEBI:18186', 'Chemical') :: ['tyrosine'] @entity1835 :: ('572', 'Gene') :: ['Bad'] @entity238 :: ('7227', 'Species') :: ['Drosophila']
@entity1261 :: (1440,Gene) :: ['granulocyte colony-stimulating factor']
