Conformational switches that control the TEC kinase – PLCγ signaling axis
Cell surface receptors such as the T-cell receptor (TCR) and B-cell receptor (BCR) engage with external stimuli to transmit information into the cell and initiate a cascade of signaling events that lead to gene expression that drives the immune response. At the heart of controlling T- and B-cell cel...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-01-01
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| Series: | Journal of Structural Biology: X |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590152422000022 |
| _version_ | 1811187908610097152 |
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| author | Jacques Lowe Raji E. Joseph Amy H. Andreotti |
| author_facet | Jacques Lowe Raji E. Joseph Amy H. Andreotti |
| author_sort | Jacques Lowe |
| collection | DOAJ |
| description | Cell surface receptors such as the T-cell receptor (TCR) and B-cell receptor (BCR) engage with external stimuli to transmit information into the cell and initiate a cascade of signaling events that lead to gene expression that drives the immune response. At the heart of controlling T- and B-cell cell signaling, phospholipase Cγ hydrolyzes membrane associated PIP2, leading to generation of the second messengers IP3 and DAG. These small molecules trigger mobilization of intracellular Ca2+ and promote transcription factor transport into the nucleus launching the adaptive immune response. The TEC family kinases are responsible for phosphorylating and activating PLCγ, and our group aims to understand mechanisms that regulate immune cell signal transduction by focusing on this kinase/phospholipase axis in T-cells and B-cells. Here, we review the current molecular level understanding of how the TEC kinases (ITK and BTK) and PLCγ1/2 are autoinhibited prior to activation of cell surface receptors, how TEC kinases are activated to specifically recognize the PLCγ substrate, and how conformational changes induced by phosphorylation trigger PLCγ activation. |
| first_indexed | 2024-04-11T14:11:28Z |
| format | Article |
| id | doaj.art-8e4f51776dd241dea5c38b325a6e6f40 |
| institution | Directory Open Access Journal |
| issn | 2590-1524 |
| language | English |
| last_indexed | 2024-04-11T14:11:28Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Structural Biology: X |
| spelling | doaj.art-8e4f51776dd241dea5c38b325a6e6f402022-12-22T04:19:42ZengElsevierJournal of Structural Biology: X2590-15242022-01-016100061Conformational switches that control the TEC kinase – PLCγ signaling axisJacques Lowe0Raji E. Joseph1Amy H. Andreotti2Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, USARoy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, USACorresponding author.; Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, USACell surface receptors such as the T-cell receptor (TCR) and B-cell receptor (BCR) engage with external stimuli to transmit information into the cell and initiate a cascade of signaling events that lead to gene expression that drives the immune response. At the heart of controlling T- and B-cell cell signaling, phospholipase Cγ hydrolyzes membrane associated PIP2, leading to generation of the second messengers IP3 and DAG. These small molecules trigger mobilization of intracellular Ca2+ and promote transcription factor transport into the nucleus launching the adaptive immune response. The TEC family kinases are responsible for phosphorylating and activating PLCγ, and our group aims to understand mechanisms that regulate immune cell signal transduction by focusing on this kinase/phospholipase axis in T-cells and B-cells. Here, we review the current molecular level understanding of how the TEC kinases (ITK and BTK) and PLCγ1/2 are autoinhibited prior to activation of cell surface receptors, how TEC kinases are activated to specifically recognize the PLCγ substrate, and how conformational changes induced by phosphorylation trigger PLCγ activation.http://www.sciencedirect.com/science/article/pii/S2590152422000022 |
| spellingShingle | Jacques Lowe Raji E. Joseph Amy H. Andreotti Conformational switches that control the TEC kinase – PLCγ signaling axis Journal of Structural Biology: X |
| title | Conformational switches that control the TEC kinase – PLCγ signaling axis |
| title_full | Conformational switches that control the TEC kinase – PLCγ signaling axis |
| title_fullStr | Conformational switches that control the TEC kinase – PLCγ signaling axis |
| title_full_unstemmed | Conformational switches that control the TEC kinase – PLCγ signaling axis |
| title_short | Conformational switches that control the TEC kinase – PLCγ signaling axis |
| title_sort | conformational switches that control the tec kinase plcγ signaling axis |
| url | http://www.sciencedirect.com/science/article/pii/S2590152422000022 |
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