IRF4 Deficiency Leads to Altered BCR Signalling Revealed by Enhanced PI3K Pathway, Decreased SHIP Expression and Defected Cytoskeletal Responses

Autor:	Alexey V. Sarapulov, Pieta K. Mattila, Minna Niemelä, Asta Laiho, Sini Junttila, Kalle-Pekka Nera, Jukka Alinikula, Minna K. Kyläniemi, Paulina Budzynska, Olli Lassila
Rok vydání:	2015
Předmět:	MAPK/ERK pathway Immunology Receptors Antigen B-Cell Biology ta3111 Cell Line Avian Proteins Gene Knockout Techniques Phosphatidylinositol 3-Kinases Plasma cell differentiation medicine Animals Syk Kinase Calcium Signaling Phosphorylation Extracellular Signal-Regulated MAP Kinases Protein kinase B Transcription factor PI3K/AKT/mTOR pathway B cell Adaptor Proteins Signal Transducing Regulation of gene expression B-Lymphocytes Intracellular Signaling Peptides and Proteins breakpoint cluster region General Medicine Protein-Tyrosine Kinases Phosphoric Monoester Hydrolases Cell biology Oncogene Protein v-akt Actin Cytoskeleton medicine.anatomical_structure Gene Expression Regulation Interferon Regulatory Factors Chickens
Zdroj:	Scandinavian Journal of Immunology. 82:418-428
ISSN:	0300-9475
DOI:	10.1111/sji.12343
Popis:	The graded expression of transcription factor interferon regulatory factor 4 (IRF4) regulates B cell development and is critical for plasma cell differentiation. However, the mechanisms, by which IRF4 elicits its crucial tasks, are largely unknown. To characterize the molecular targets of IRF4 in B cells, we established an IRF4-deficient DT40 B cell line. We found that in the absence of IRF4, the expression of several molecules involved in BCR signalling was altered. For example, the expression of B cell adaptor for PI3K (BCAP) was upregulated, whereas the SHIP (SH2-containing Inositol 5?-Phosphatase) expression was downregulated. These molecular unbalances were accompanied by increased BCR-induced calcium signalling, attenuated B cell linker protein (BLNK) and ERK activity and enhanced activity of PI3K/protein kinase B (Akt) pathway. Further, the IRF4-deficient cells showed dramatically diminished cytoskeletal responses to anti-IgM cross-linking. Our results show that IRF4 has an important role in the regulation of BCR signalling and help to shed light on the molecular mechanisms of B cell development and germinal centre response.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::66d78613685290892d71f07572881281 https://doi.org/10.1111/sji.12343 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.