Hepatocyte growth factor regulated tyrosine kinase substrate in the peripheral development and function of B-cells

Takayuki Nagata, Kazuko Murata, Ryo Murata, Shu Lan Sun, Yutaro Saito, Shuhei Yamaga, Nobuyuki Tanaka, Keiichi Tamai, Kunihiko Moriya, Noriyuki Kasai, Kazuo Sugamura, Naoto Ishii

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate (Hrs) is a vesicular sorting protein that functions as one of the endosomal-sorting proteins required for transport (ESCRT). Hrs, which binds to ubiquitinated proteins through its ubiquitin-interacting motif (UIM), contributes to the lysosomal transport and degradation of ubiquitinated membrane proteins. However, little is known about the relationship between B-cell functions and ESCRT proteins in vivo. Here we examined the immunological roles of Hrs in B-cell development and functions using B-cell-specific Hrs-deficient (Hrs flox/flox;mb1cre/+:Hrs-cKO) mice, which were generated using a cre-LoxP recombination system. Hrs deficiency in B-cells significantly reduced T-cell-dependent antibody production in vivo and impaired the proliferation of B-cells treated in vitro with an anti-IgM monoclonal antibody but not with LPS. Although early development of B-cells in the bone marrow was normal in Hrs-cKO mice, there was a significant decrease in the number of the peripheral transitional B-cells and marginal zone B-cells in the spleen of Hrs-cKO mice. These results indicate that Hrs plays important roles during peripheral development and physiological functions of B lymphocytes.

Original languageEnglish
Pages (from-to)351-356
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number2
Publication statusPublished - 2014 Jan 10


  • B-cell
  • BCR
  • Hrs


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