TY - JOUR
T1 - A transmembrane osteoclastic protein-tyrosine phosphatase regulates osteoclast activity in part by promoting osteoclast survival through c-Src-dependent activation of NFκB and JNK2
AU - Amoui, Mehran
AU - Sheng, Matilda H.C.
AU - Chen, Shin Tai
AU - Baylink, David J.
AU - Lau, K. H.William
N1 - Funding Information:
This work was supported in part by a Merit Review provided by the Office of Research and Development, Medical Research Service, Department of Veteran Affairs. All work was performed in facilities provided by the Department of Veterans Affairs. The authors acknowledge the excellent technical assistance from Ms. Belinda Nestor and Ms. Virginia Stiffel.
PY - 2007/7/1
Y1 - 2007/7/1
N2 - This study evaluated the effects of overexpression of wild-type (WT) or phosphatase-deficient (PD) mutant of an osteoclastic protein-tyrosine phosphatase (PTP-oc) in RAW/C4 cells. Osteoclast-like cells derived from WT-PTP-oc overexpressing clones increased, while those derived from PD-PTP-oc expressing clones decreased, their resorption activity. WT-PTP-oc clones had lower apoptosis, lower caspase 3/7 activity, reduced c-Src tyr-527 phosphorylation (PY527) and IκBα cellular levels, and increased NFκB activation and JNK phosphorylation. Overexpression of PD-PTP-oc or PTP-oc siRNA treatment increased apoptosis, caspase 3/7 activity, PY527 and IκBα levels, and decreased NFκB and JNK2 activation. Inhibition of the c-Src kinase blocked the PTP-oc-mediated NFκB and JNK2 activation. Blocking the NFκB activation had no effect on the JNK2 activation. Inhibiting the NFκB and/or JNK2 pathway prevented the PTP-oc-mediated reduction in apoptosis. In conclusion, PTP-oc activates osteoclast activity in part by promoting osteoclast survival through the PTP-oc-mediated c-Src-dependent activation of NFκB and JNK2. © 2007 Elsevier Inc. All rights reserved.
AB - This study evaluated the effects of overexpression of wild-type (WT) or phosphatase-deficient (PD) mutant of an osteoclastic protein-tyrosine phosphatase (PTP-oc) in RAW/C4 cells. Osteoclast-like cells derived from WT-PTP-oc overexpressing clones increased, while those derived from PD-PTP-oc expressing clones decreased, their resorption activity. WT-PTP-oc clones had lower apoptosis, lower caspase 3/7 activity, reduced c-Src tyr-527 phosphorylation (PY527) and IκBα cellular levels, and increased NFκB activation and JNK phosphorylation. Overexpression of PD-PTP-oc or PTP-oc siRNA treatment increased apoptosis, caspase 3/7 activity, PY527 and IκBα levels, and decreased NFκB and JNK2 activation. Inhibition of the c-Src kinase blocked the PTP-oc-mediated NFκB and JNK2 activation. Blocking the NFκB activation had no effect on the JNK2 activation. Inhibiting the NFκB and/or JNK2 pathway prevented the PTP-oc-mediated reduction in apoptosis. In conclusion, PTP-oc activates osteoclast activity in part by promoting osteoclast survival through the PTP-oc-mediated c-Src-dependent activation of NFκB and JNK2. © 2007 Elsevier Inc. All rights reserved.
KW - Apoptosis
KW - JNK
KW - Osteoclasts
KW - Protein-tyrosine phosphatase
KW - Survival
KW - c-Src
KW - Cell Survival/physiology
KW - Mitogen-Activated Protein Kinase 9/physiology
KW - NF-kappa B/physiology
KW - Proto-Oncogene Proteins pp60(c-src)/physiology
KW - Protein Tyrosine Phosphatases/physiology
KW - Bone Resorption/physiopathology
KW - Animals
KW - Apoptosis/physiology
KW - Phosphotyrosine/metabolism
KW - Cell Differentiation
KW - Mice
KW - RNA, Small Interfering/pharmacology
KW - Osteoclasts/physiology
UR - https://www.scopus.com/pages/publications/34249941912
UR - https://www.scopus.com/pages/publications/34249941912#tab=citedBy
UR - https://www.mendeley.com/catalogue/3b00041c-895c-36d1-bb57-8b9d55fa63fc/
U2 - 10.1016/j.abb.2007.02.025
DO - 10.1016/j.abb.2007.02.025
M3 - Article
C2 - 17400176
SN - 0003-9861
VL - 463
SP - 47
EP - 59
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
IS - 1
ER -