AlphaPIX Rho GTPase guanine nucleotide exchange factor regulates lymphocyte functions and antigen receptor signaling.
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AlphaPIX Rho GTPase guanine nucleotide exchange factor regulates lymphocyte functions and antigen receptor signaling. / Missy, Karine; Hu, Bin; Schilling, Kerstin; Harenberg, Anke; Sakk, Vadim; Kuchenbecker, Kerstin; Kutsche, Kerstin; Fischer, Klaus-Dieter.
in: MOL CELL BIOL, Jahrgang 28, Nr. 11, 11, 2008, S. 3776-3789.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - AlphaPIX Rho GTPase guanine nucleotide exchange factor regulates lymphocyte functions and antigen receptor signaling.
AU - Missy, Karine
AU - Hu, Bin
AU - Schilling, Kerstin
AU - Harenberg, Anke
AU - Sakk, Vadim
AU - Kuchenbecker, Kerstin
AU - Kutsche, Kerstin
AU - Fischer, Klaus-Dieter
PY - 2008
Y1 - 2008
N2 - AlphaPIX is a Rho GTPase guanine nucleotide exchange factor domain-containing signaling protein that associates with other proteins involved in cytoskeletal-membrane complexes. It has been shown that PIX proteins play roles in some immune cells, including neutrophils and T cells. In this study, we report the immune system phenotype of alphaPIX knockout mice. We extended alphaPIX expression experiments and found that whereas alphaPIX was specific to immune cells, its homolog betaPIX was expressed in a wider range of cells. Mice lacking alphaPIX had reduced numbers of mature lymphocytes and defective immune responses. Antigen receptor-directed proliferation of alphaPIX(-) T and B cells was also reduced, but basal migration was enhanced. Accompanying these defects, formation of T-cell-B-cell conjugates and recruitment of PAK and Lfa-1 integrin to the immune synapse were impaired in the absence of alphaPIX. Proximal antigen receptor signaling was largely unaffected, with the exception of reduced phosphorylation of PAK and expression of GIT2 in both T cells and B cells. These results reveal specific roles for alphaPIX in the immune system and suggest that redundancy with betaPIX precludes a more severe immune phenotype.
AB - AlphaPIX is a Rho GTPase guanine nucleotide exchange factor domain-containing signaling protein that associates with other proteins involved in cytoskeletal-membrane complexes. It has been shown that PIX proteins play roles in some immune cells, including neutrophils and T cells. In this study, we report the immune system phenotype of alphaPIX knockout mice. We extended alphaPIX expression experiments and found that whereas alphaPIX was specific to immune cells, its homolog betaPIX was expressed in a wider range of cells. Mice lacking alphaPIX had reduced numbers of mature lymphocytes and defective immune responses. Antigen receptor-directed proliferation of alphaPIX(-) T and B cells was also reduced, but basal migration was enhanced. Accompanying these defects, formation of T-cell-B-cell conjugates and recruitment of PAK and Lfa-1 integrin to the immune synapse were impaired in the absence of alphaPIX. Proximal antigen receptor signaling was largely unaffected, with the exception of reduced phosphorylation of PAK and expression of GIT2 in both T cells and B cells. These results reveal specific roles for alphaPIX in the immune system and suggest that redundancy with betaPIX precludes a more severe immune phenotype.
M3 - SCORING: Zeitschriftenaufsatz
VL - 28
SP - 3776
EP - 3789
JO - MOL CELL BIOL
JF - MOL CELL BIOL
SN - 0270-7306
IS - 11
M1 - 11
ER -
