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 Lossos

Research output: Contribution to journalArticle

18 Citations (Scopus)

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

Fingerprint

Guanine Nucleotide Exchange Factors
Germinal Center
Cell Movement
Lymphoma
Lymphoma, Large B-Cell, Diffuse
Modulation
Hodgkin Disease
Molecular Motor Proteins
Proteins
Lymphocytes
Guanosine Triphosphate
Catalytic Domain
Genes
Chemical activation
Cells
Survival

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

HGAL, a germinal center specific protein, decreases lymphoma cell motility by modulation of the RhoA signaling pathway. / Jiang, Xiaoyu; Lu, Xiaoqing; McNamara, George; Liu, Xiaofei; Cubedo, Elena; Sarosiek, Kristopher A.; Sánchez-García, Isidro; Helfman, David M.; Lossos, Izidore.

In: Blood, Vol. 116, No. 24, 09.12.2010, p. 5217-5227.

Research output: Contribution to journalArticle

Jiang, X, Lu, X, McNamara, G, Liu, X, Cubedo, E, Sarosiek, KA, Sánchez-García, I, Helfman, DM & Lossos, I 2010, 'HGAL, a germinal center specific protein, decreases lymphoma cell motility by modulation of the RhoA signaling pathway', Blood, vol. 116, no. 24, pp. 5217-5227. https://doi.org/10.1182/blood-2010-04-281568
Jiang, Xiaoyu ; Lu, Xiaoqing ; McNamara, George ; Liu, Xiaofei ; Cubedo, Elena ; Sarosiek, Kristopher A. ; Sánchez-García, Isidro ; Helfman, David M. ; Lossos, Izidore. / HGAL, a germinal center specific protein, decreases lymphoma cell motility by modulation of the RhoA signaling pathway. In: Blood. 2010 ; Vol. 116, No. 24. pp. 5217-5227.
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AU - Cubedo, Elena

AU - Sarosiek, Kristopher A.

AU - Sánchez-García, Isidro

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