TY - JOUR
T1 - Requirement of PEST domain tyrosine phosphatase PEP in B cell antigen receptor-induced growth arrest and apoptosis
AU - Hasegawa, Kiminori
AU - Yajima, Hiroaki
AU - Katagiri, Tatsuo
AU - Ogimoto, Mami
AU - Arimura, Yutaka
AU - Mitomo, Katsuyuki
AU - Mashima, Keisuke
AU - Mizuno, Kazuya
AU - Yakura, Hidetaka
PY - 1999
Y1 - 1999
N2 - Signaling events leading to B cell growth or apoptosis are beginning to be unravelled, but detailed information is still lacking. To identify signaling molecules involved in B cell antigen receptor (BCR)-initiated pathways, we used the immature B cell line, WEHI-231, to investigate protein tyrosine phosphatases (PTP) whose expression was modulated by BCR ligation. Among the PTP cloned by reverse transcription-PCR, mRNA expression of the proline-, glutamic acid-, serine- and threonine-rich (PEST) domain phosphatase (PEP) was selectively elevated 3.1-fold within 3 h after anti-IgM antibody stimulation. In contrast, expression of another PEST domain phosphatase, PTP-PEST, was unaffected. Western blot analysis revealed that 71% of PEP was located in the cytosolic fraction, while 29% was in the membrane fraction. To examine the direct contribution made by PEP to BCR-initiated signal transduction, we transfected an antisense PEP cDNA into WEHI-231 cells. Two stable clones were established in which PEP expression was reduced by 34% and 47%, respectively. Strikingly, BCR-mediated inhibition of DNA synthesis was significantly rescued in the clones, and G1 phase cell cycle arrest and apoptosis were almost completely ablated. Considered collectively, these results indicate that PEP is a positive, crucial regulator in determining B cell fate triggered by BCR engagement.
AB - Signaling events leading to B cell growth or apoptosis are beginning to be unravelled, but detailed information is still lacking. To identify signaling molecules involved in B cell antigen receptor (BCR)-initiated pathways, we used the immature B cell line, WEHI-231, to investigate protein tyrosine phosphatases (PTP) whose expression was modulated by BCR ligation. Among the PTP cloned by reverse transcription-PCR, mRNA expression of the proline-, glutamic acid-, serine- and threonine-rich (PEST) domain phosphatase (PEP) was selectively elevated 3.1-fold within 3 h after anti-IgM antibody stimulation. In contrast, expression of another PEST domain phosphatase, PTP-PEST, was unaffected. Western blot analysis revealed that 71% of PEP was located in the cytosolic fraction, while 29% was in the membrane fraction. To examine the direct contribution made by PEP to BCR-initiated signal transduction, we transfected an antisense PEP cDNA into WEHI-231 cells. Two stable clones were established in which PEP expression was reduced by 34% and 47%, respectively. Strikingly, BCR-mediated inhibition of DNA synthesis was significantly rescued in the clones, and G1 phase cell cycle arrest and apoptosis were almost completely ablated. Considered collectively, these results indicate that PEP is a positive, crucial regulator in determining B cell fate triggered by BCR engagement.
KW - Antisense strategy
KW - Apoptosis
KW - B cell receptor signaling
KW - PEP
UR - http://www.scopus.com/inward/record.url?scp=0033016466&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1521-4141(199903)29:03<887::AID-IMMU887>3.0.CO;2-9
DO - 10.1002/(SICI)1521-4141(199903)29:03<887::AID-IMMU887>3.0.CO;2-9
M3 - 学術論文
C2 - 10092092
AN - SCOPUS:0033016466
SN - 0014-2980
VL - 29
SP - 887
EP - 896
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 3
ER -