The role of activin type I receptors in activin A-induced growth arrest and apoptosis in mouse B-cell hybridoma cells.
Activins transduce their signals by binding to activin type I receptors and activin type II receptors, both of which contain a serine/threonine kinase domain. In this study, we established stable transfectants expressing two types of activin receptors, ActRI and ActRIB, to clarify the role of these receptors in activin signalling for growth inhibition in HS-72 mouse B-cell hybridoma cells. Over-expression of ActRI suppressed activin A-induced cell-cycle arrest in the G1 phase caused by inhibition of retinoblastoma protein phosphorylation through induction of p21CIP1/WAF1, a cyclin-dependent kinase inhibitor, and subsequent apoptosis. In contrast, HS-72 clones that over-expressed ActRIB significantly facilitated activin A-induced apoptosis. These results indicate that ActRI and ActRIB are distinct from each other and that the ActRI/ActRIB expression ratio could regulate cell-cycle arrest in the G1 phase and subsequent apoptosis in HS-72 cells induced by activin A.
Hashimoto
O
O
Department of Oral Science, National Institute of Infectious Diseases, Tokyo, Japan.
Yamato
K
K
Koseki
T
T
Ohguchi
M
M
Ishisaki
A
A
Shoji
H
H
Nakamura
T
T
Hayashi
Y
Y
Sugino
H
H
Nishihara
T
T
D030201:Activin Receptors, Type I; D028341:Activins; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001402:B-Lymphocytes; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D016193:G1 Phase; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D006825:Hybridomas; D007265:Inhibins / Q000494:pharmacology* / Q000502:physiology; D051379:Mice; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D006133:Growth Substances; D017978:Receptors, Growth Factor; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein; D028341:Activins; D007265:Inhibins; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I