Enzyme Is the Name—Adapter Is the Game
Abstract
1. Introduction
2. Bruton’s Tyrosine Kinase (BTK) Exerts Important Enzymatic as Well as Adapter Functions in Immune Cells
3. The p110γ Isotype of Phosphatidylinositol 3-Kinase (PI3K) Enzymatically Controls Chemotaxis and Uses Its Adapter Function for Regulating cAMP Levels
4. The Hemopoietic Lipid Phosphatase SH2-Containing Inositol Phosphatase 1 (SHIP1) Controls RAS Activity by Means of Differential Adapter Functions
5. Examples from Receptor Tyrosine Kinase (RTK)-MAPK Pathways
5.1. The Pseudokinase HER3/ErbB3 Contributes to Activation of EGFR Family Members in a Kinase-Independent Manner
5.2. The Tyrosine Phosphatase SHP2 Exerts Signaling Functions Independent of Its Catalytic Activity
5.3. Rapidly Accelerated Fibrosarcoma (RAF) and Kinase Suppressor of RAS (KSR) Proteins: Moonlighting and Allostery
Protein | Role as Enzyme | Role as Adapter | Ref. |
---|---|---|---|
BTK | Phosphorylation/activation of PLCγ | Tumor suppressor function Membrane recruitment of PIP5Ks causing PI45P2 production | [16,17,18] |
ITK | Phosphorylation/activation of PLCγ | TCR/CD3-triggered actin polymerization | [30] |
PI3K (p110γ) | Phosphorylation of PI45P2 to yield PIP3 Regulation of leukocyte migration and inflammation | Constitutive interaction with PDE3B and promotion of PDE3B activity (cAMP hydrolysis) in cardiomyocytes | [34,37] |
SHIP1 | Hydrolysis of PIP3 to yield PI34P2 Inhibition of PKB activation and Ca2+ mobilization upon BCR-FcγRIIB crosslinking | Attenuation of RAS activation by GRB2-SOS competition Inhibition of RAS by DOK1-RASGAP1 recruitment Attenuation of NOD2-induced NFκB activation by interacting with XIAP | [38,44,45,47,49,50] |
HER3/ ErbB3 | Naturally inactive kinase (pseudokinase) or kinase with low intrinsic enzymatic activity | Allosteric transactivator of catalytically competent EGFR family members, most notably HER2/ErbB2; adaptor, phospho-tyrosine residues as docking sites for PI3K recruitment | [73,74,76] |
SHP2 | Protein tyrosine phosphatase | Protection of phosphotyrosine residues by tandem SH2 domain against dephosphorylation | [87] |
RAF1 | Protein serine/threonine kinase | Various adaptor functions, see text for details | [90,91,92,93,94,95] |
KSR1 | Naturally inactive kinase (pseudokinase) or kinase with low intrinsic enzymatic activity | Scaffolding functions for the RAF/MEK/ERK pathway; allosteric transactivator for BRAF | [100] |
6. Pharmacological Implications
7. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Huber, M.; Brummer, T. Enzyme Is the Name—Adapter Is the Game. Cells 2024, 13, 1249. https://doi.org/10.3390/cells13151249
Huber M, Brummer T. Enzyme Is the Name—Adapter Is the Game. Cells. 2024; 13(15):1249. https://doi.org/10.3390/cells13151249
Chicago/Turabian StyleHuber, Michael, and Tilman Brummer. 2024. "Enzyme Is the Name—Adapter Is the Game" Cells 13, no. 15: 1249. https://doi.org/10.3390/cells13151249
APA StyleHuber, M., & Brummer, T. (2024). Enzyme Is the Name—Adapter Is the Game. Cells, 13(15), 1249. https://doi.org/10.3390/cells13151249