HGAL, a germinal center specific protein, decreases lymphoma cell motility by modulation of the RhoA signaling pathway

Xiaoyu Jiang, Xiaoqing Lu, George McNamara, Xiaofei Liu, Elena Cubedo, Kristopher A. Sarosiek, Isidro Sánchez-García, David M. Helfman, Izidore S. Lossos

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

HGAL is a germinal center (GC)-specific gene that negatively regulates lymphocyte motility and whose expression predicts improved survival of patients with diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma (cHL). We demonstrate that HGAL serves as a regulator of the RhoA signaling pathway. HGAL enhances activation of RhoA and its down-stream effectors by a novel mechanism - direct binding to the catalytic DH-domain of the RhoA-specific guanine nucleotide exchange factors (RhoGEFs) PDZ-RhoGEF and LARG that stimulate the GDP-GTP exchange rate of RhoA. We delineate the structural domain of HGAL that mediates its interaction with the PDZ-RhoGEF protein. These observations reveal a novel molecular mechanism underlying the inhibitory effects of GC-specific HGAL protein on the motility of GC-derived lymphoma cells. This mechanism may underlie the limited dissemination and better outcome of patients with HGAL-expressing DLBCL and cHL.

Original languageEnglish (US)
Pages (from-to)5217-5227
Number of pages11
JournalBlood
Volume116
Issue number24
DOIs
StatePublished - Dec 9 2010

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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