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Lipopolysaccharide‐responsive beige‐like anchor acts as a cAMP‐dependent protein kinase anchoring protein in B cells
Author(s) -
MorenoCoroidia Carolina,
LopezOrtega Orestes,
Flores Hermenegildo Jose Mizael,
BerronRuiz Laura,
RodriguezAlba Juan Carlos,
SantosArgumedo Leopoldo,
LopezHerrera Gabriela
Publication year - 2020
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12922
Subject(s) - protein kinase a , anchoring , microbiology and biotechnology , lipopolysaccharide , kinase , biology , chemistry , immunology , psychology , social psychology
Lipopolysaccharide (LPS)‐responsive beige‐like anchor (LRBA) protein was initially described as a monogenetic cause for common variable immune deficiency, a syndrome characterized by low levels of B cells, defects in memory B cell differentiation and hypogammaglobulinaemia. LRBA was identified as an LPS up‐regulated gene in B cells, macrophages and T cells. LRBA weighs 320 kDa and has 2863 amino acids. Its sequence contains multiple domains, suggesting that LRBA can act as a scaffolding protein. It contains two putative binding sites for cAMP‐dependent kinase (PKA) regulatory subunits, suggesting this protein can act as A‐kinase anchor protein (AKAP); however, physical interactions involving LRBA and PKA have not been demonstrated to date, and functional roles for such interactions are unexplored. In this work, we investigated physical interactions involving LRBA with regulatory subunits of PKA in human B cell lines and primary human B cells. PKA is a holoenzyme composed of two regulatory subunits, which can be RIα, RIβ, RIIα or RIIβ, and two catalytic subunits, Cα or Cβ. We co‐immunoprecipitated LRBA using Ramos B cell lymphoma cells and observed that LRBA interacts with RIIβ. Interestingly, St‐Ht31, an inhibitory peptide that disrupts AKAP interactions with regulatory subunits, reduced the amount of interacting protein. Furthermore, in primary human B cells, LRBA was induced after CD40L and IL‐4 stimulation, and under such activation, we found that LRBA interacts with RIIα and RIIβ, suggesting that LRBA acts as an AKAP and binds RII subunits. Interestingly, we also identified that LRBA interacts with activation‐induced cytidine deaminase in primary B cells, suggesting that it is involved in B cell function.