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@article{Sprangers:2006:10.1038/sj.onc.1209510,
author = {Sprangers, M and Feldhahn, N and Herzog, S and Hansmann, ML and Reppel, M and Hescheler, J and Jumaa, H and Siebert, R and Muschen, M},
doi = {10.1038/sj.onc.1209510},
journal = {Oncogene},
pages = {5056--5062},
title = {The SRC family kinase LYN redirects B cell receptor signaling in human SLP65-deficient B cell lymphoma cells},
url = {http://dx.doi.org/10.1038/sj.onc.1209510},
volume = {25},
year = {2006}
}

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TY  - JOUR
AB  - SLP65 represents a critical component in (pre-) B cell receptor signal transduction but is compromised in a subset of pre-B cell-derived acute lymphoblastic leukemia. Based on these findings, we investigated (i.) whether SLP65-deficiency also occurs in mature B cell-derived lymphoma and (ii.) whether SLP65-deficient B cell lymphoma cells use an alternative B cell receptor signaling pathway in the absence of SLP65. Indeed, expression of SLP65 protein was also missing in a fraction of B cell lymphoma cases. While SLP65 is essential for B cell receptor-induced Ca2+ mobilization in normal B cells, B cell receptor engagement in SLP65-deficient as compared to SLP65-reconstituted B cell lymphoma cells resulted in an accelerated yet shortlived Ca2+-signal. B cell receptor engagement of SLP65-deficient lymphoma cells involves SRC kinase activation, which is critical for B cell receptor-dependent Ca2+-mobilisation in the absence but not in the presence of SLP65. As shown by RNA interference, the SRC kinase LYN is required for B cell receptor-induced Ca2+ release in SLP65-deficient B cell lymphoma cells but dispensable after SLP65-reconstitution. B cell receptor engagement in SLP65-deficient B cell lymphoma cells also resulted in tyrosine-phosphorylation of the proliferation- and survival-related MAPK1 and STAT5 molecules, which was sensitive to silencing of the SRC kinase LYN. Inhibition of SRC kinase activity resulted in growth arrest and cell death specifically in SLP65-deficient lymphoma cells. These findings indicate that LYN can short-circuit conventional B cell receptor signaling in SLP65-deficient B cell lymphoma cells and thereby promote activation of survival and proliferation-related molecules.
AU  - Sprangers,M
AU  - Feldhahn,N
AU  - Herzog,S
AU  - Hansmann,ML
AU  - Reppel,M
AU  - Hescheler,J
AU  - Jumaa,H
AU  - Siebert,R
AU  - Muschen,M
DO  - 10.1038/sj.onc.1209510
EP  - 5062
PY  - 2006///
SN  - 0950-9232
SP  - 5056
TI  - The SRC family kinase LYN redirects B cell receptor signaling in human SLP65-deficient B cell lymphoma cells
T2  - Oncogene
UR  - http://dx.doi.org/10.1038/sj.onc.1209510
UR  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16568084
VL  - 25
ER  -

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