Impaired lymphocyte trafficking in mice deficient in the kinase activity of PKN1
Abstract Knock-in mice lacking PKN1 kinase activity were generated by introducing a T778A point mutation in the catalytic domain. PKN1[T778A] mutant mice developed to adulthood without apparent external abnormalities, but exhibited lower T and B lymphocyte counts in the peripheral blood than those o...
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Nature Portfolio
2017
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oai:doaj.org-article:a3d5289eeb8f44ccac821f81a0e780452021-12-02T12:32:40ZImpaired lymphocyte trafficking in mice deficient in the kinase activity of PKN110.1038/s41598-017-07936-92045-2322https://doaj.org/article/a3d5289eeb8f44ccac821f81a0e780452017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07936-9https://doaj.org/toc/2045-2322Abstract Knock-in mice lacking PKN1 kinase activity were generated by introducing a T778A point mutation in the catalytic domain. PKN1[T778A] mutant mice developed to adulthood without apparent external abnormalities, but exhibited lower T and B lymphocyte counts in the peripheral blood than those of wild-type (WT) mice. T and B cell development proceeded in an apparently normal fashion in bone marrow and thymus of PKN1[T778A] mice, however, the number of T and B cell counts were significantly higher in the lymph nodes and spleen of mutant mice in those of WT mice. After transfusion into WT recipients, EGFP-labelled PKN1[T778A] donor lymphocytes were significantly less abundant in the peripheral circulation and more abundant in the spleen and lymph nodes of recipient mice compared with EGFP-labelled WT donor lymphocytes, likely reflecting lymphocyte sequestration in the spleen and lymph nodes in a cell-autonomous fashion. PKN1[T778A] lymphocytes showed significantly lower chemotaxis towards chemokines and sphingosine 1-phosphate (S1P) than WT cells in vitro. The biggest migration defect was observed in response to S1P, which is essential for lymphocyte egress from secondary lymphoid organs. These results reveal a novel role of PKN1 in lymphocyte migration and localization.Rana MashudAkira NomachiAkihide HayakawaKoji KubouchiSally DannoTakako HirataKazuhiko MatsuoTakashi NakayamaRyosuke SatohReiko SugiuraManabu AbeKenji SakimuraShigeharu WakanaHiroyuki OhsakiShingo KamoshidaHideyuki MukaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017) |
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Medicine R Science Q Rana Mashud Akira Nomachi Akihide Hayakawa Koji Kubouchi Sally Danno Takako Hirata Kazuhiko Matsuo Takashi Nakayama Ryosuke Satoh Reiko Sugiura Manabu Abe Kenji Sakimura Shigeharu Wakana Hiroyuki Ohsaki Shingo Kamoshida Hideyuki Mukai Impaired lymphocyte trafficking in mice deficient in the kinase activity of PKN1 |
| description |
Abstract Knock-in mice lacking PKN1 kinase activity were generated by introducing a T778A point mutation in the catalytic domain. PKN1[T778A] mutant mice developed to adulthood without apparent external abnormalities, but exhibited lower T and B lymphocyte counts in the peripheral blood than those of wild-type (WT) mice. T and B cell development proceeded in an apparently normal fashion in bone marrow and thymus of PKN1[T778A] mice, however, the number of T and B cell counts were significantly higher in the lymph nodes and spleen of mutant mice in those of WT mice. After transfusion into WT recipients, EGFP-labelled PKN1[T778A] donor lymphocytes were significantly less abundant in the peripheral circulation and more abundant in the spleen and lymph nodes of recipient mice compared with EGFP-labelled WT donor lymphocytes, likely reflecting lymphocyte sequestration in the spleen and lymph nodes in a cell-autonomous fashion. PKN1[T778A] lymphocytes showed significantly lower chemotaxis towards chemokines and sphingosine 1-phosphate (S1P) than WT cells in vitro. The biggest migration defect was observed in response to S1P, which is essential for lymphocyte egress from secondary lymphoid organs. These results reveal a novel role of PKN1 in lymphocyte migration and localization. |
| format |
article |
| author |
Rana Mashud Akira Nomachi Akihide Hayakawa Koji Kubouchi Sally Danno Takako Hirata Kazuhiko Matsuo Takashi Nakayama Ryosuke Satoh Reiko Sugiura Manabu Abe Kenji Sakimura Shigeharu Wakana Hiroyuki Ohsaki Shingo Kamoshida Hideyuki Mukai |
| author_facet |
Rana Mashud Akira Nomachi Akihide Hayakawa Koji Kubouchi Sally Danno Takako Hirata Kazuhiko Matsuo Takashi Nakayama Ryosuke Satoh Reiko Sugiura Manabu Abe Kenji Sakimura Shigeharu Wakana Hiroyuki Ohsaki Shingo Kamoshida Hideyuki Mukai |
| author_sort |
Rana Mashud |
| title |
Impaired lymphocyte trafficking in mice deficient in the kinase activity of PKN1 |
| title_short |
Impaired lymphocyte trafficking in mice deficient in the kinase activity of PKN1 |
| title_full |
Impaired lymphocyte trafficking in mice deficient in the kinase activity of PKN1 |
| title_fullStr |
Impaired lymphocyte trafficking in mice deficient in the kinase activity of PKN1 |
| title_full_unstemmed |
Impaired lymphocyte trafficking in mice deficient in the kinase activity of PKN1 |
| title_sort |
impaired lymphocyte trafficking in mice deficient in the kinase activity of pkn1 |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/a3d5289eeb8f44ccac821f81a0e78045 |
| work_keys_str_mv |
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| _version_ |
1718393996929138688 |