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CaMK4 is a downstream effector of the α1G T-type calcium channel to determine the angiogenic potential of pulmonary microvascular endothelial cells.
Zheng, Zhen; Wang, Xuelin; Wang, Yuxia; King, Judy A C; Xie, Peilin; Wu, Songwei.
Affiliation
  • Zheng Z; Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
  • Wang X; Department of Respiratory and Critical Care Medicine, Henan Provincial People's Hospital, Zhengzhou, China.
  • Wang Y; Department of Anesthesiology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • King JAC; Department of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center - Shreveport, Shreveport, Louisiana.
  • Xie P; Department of Anesthesiology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • Wu S; Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
Am J Physiol Cell Physiol ; 321(6): C964-C977, 2021 12 01.
Article in En | MEDLINE | ID: mdl-34586897
Pulmonary microvascular endothelial cells (PMVECs) uniquely express an α1G-subtype of voltage-gated T-type Ca2+ channel. We have previously revealed that the α1G channel functions as a background Ca2+ entry pathway that is critical for the cell proliferation, migration, and angiogenic potential of PMVECs, a novel function attributed to the coupling between α1G-mediated Ca2+ entry and constitutive Akt phosphorylation and activation. Despite this significance, mechanism(s) that link the α1G-mediated Ca2+ entry to Akt phosphorylation remain incompletely understood. In this study, we demonstrate that Ca2+/calmodulin-dependent protein kinase (CaMK) 4 serves as a downstream effector of the α1G-mediated Ca2+ entry to promote the angiogenic potential of PMVECs. Notably, CaMK2 and CaMK4 are both expressed in PMVECs. Pharmacological blockade or genetic knockdown of the α1G channel led to a significant reduction in the phosphorylation level of CaMK4 but not the phosphorylation level of CaMK2. Pharmacological inhibition as well as genetic knockdown of CaMK4 significantly decreased cell proliferation, migration, and network formation capacity in PMVECs. However, CaMK4 inhibition or knockdown did not alter Akt phosphorylation status in PMVECs, indicating that α1G/Ca2+/CaMK4 is independent of the α1G/Ca2+/Akt pathway in sustaining the cells' angiogenic potential. Altogether, these findings suggest a novel α1G-CaMK4 signaling complex that regulates the Ca2+-dominated angiogenic potential in PMVECs.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Calcium / Neovascularization, Physiologic / Calcium Signaling / Calcium Channels, T-Type / Endothelial Cells / Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Microvessels / Lung Limits: Animals Language: En Journal: Am J Physiol Cell Physiol Journal subject: FISIOLOGIA Year: 2021 Document type: Article Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Calcium / Neovascularization, Physiologic / Calcium Signaling / Calcium Channels, T-Type / Endothelial Cells / Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Microvessels / Lung Limits: Animals Language: En Journal: Am J Physiol Cell Physiol Journal subject: FISIOLOGIA Year: 2021 Document type: Article Country of publication: United States