Verdin, P. Top companies and drugs by sales in 2023. Nat. Rev. Drug. Discov. 23, 240 (2024).

Article  CAS  PubMed  Google Scholar 

June, C. H. & Sadelain, M. Chimeric antigen receptor therapy. N. Engl. J. Med. 379, 64–73 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hegde, P. S. & Chen, D. S. Top 10 challenges in cancer immunotherapy. Immunity 52, 17–35 (2020).

Article  CAS  PubMed  Google Scholar 

Billadeau, D. D. & Leibson, P. J. ITAMs versus ITIMs: striking a balance during cell regulation. J. Clin. Invest. 109, 161–168 (2002).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yang, W. et al. Dynamic regulation of CD28 conformation and signaling by charged lipids and ions. Nat. Struct. Mol. Biol. 24, 1081–1092 (2017).

Article  CAS  PubMed  Google Scholar 

Xu, C. et al. Regulation of T cell receptor activation by dynamic membrane binding of the CD3ε cytoplasmic tyrosine-based motif. Cell 135, 702–713 (2008). This paper demonstrates that the electrostatic interactions between the BRS and acidic lipids sequester the adjacent tyrosine motif within the membrane.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dobbins, J. et al. Binding of the cytoplasmic domain of CD28 to the plasma membrane inhibits lck recruitment and signaling. Sci. Signal. 9, ra75 (2016).

Article  PubMed  PubMed Central  Google Scholar 

Deford-Watts, L. M. et al. The cytoplasmic tail of the T cell receptor CD3ε subunit contains a phospholipid-binding motif that regulates T cell functions. J. Immunol. 183, 1055–1064 (2009).

Article  CAS  PubMed  Google Scholar 

Li, L. et al. Ionic CD3–Lck interaction regulates the initiation of T-cell receptor signaling. Proc. Natl Acad. Sci. USA 114, E5891–E5899 (2017).

CAS  PubMed  PubMed Central  Google Scholar 

Wu, W. et al. Multiple signaling roles of CD3ε and its application in CAR-T cell therapy. Cell 182, 855–871 e823 (2020). This paper reports TCR–CD3 phosphorylation patterns and a rational design of CD3ε-based CARs.

Article  CAS  PubMed  Google Scholar 

Aivazian, D. & Stern, L. J. Phosphorylation of T cell receptor ζ is regulated by a lipid dependent folding transition. Nat. Struct. Biol. 7, 1023–1026 (2000).

Article  CAS  PubMed  Google Scholar 

Zhang, H., Cordoba, S. P., Dushek, O. & van der Merwe, P. A. Basic residues in the T-cell receptor ζ cytoplasmic domain mediate membrane association and modulate signaling. Proc. Natl Acad. Sci. USA 108, 19323–19328 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

DeFord-Watts, L. M. et al. The CD3 ζ subunit contains a phosphoinositide-binding motif that is required for the stable accumulation of TCR–CD3 complex at the immunological synapse. J. Immunol. 186, 6839–6847 (2011).

Article  CAS  PubMed  Google Scholar 

Chen, X. et al. Acidic phospholipids govern the enhanced activation of IgG-B cell receptor. Nat. Commun. 6, 8552 (2015).

Article  CAS  PubMed  Google Scholar 

Wen, M. et al. PD-L1 degradation is regulated by electrostatic membrane association of its cytoplasmic domain. Nat. Commun. 12, 5106 (2021). This paper demonstrates that the electrostatic interactions between the BRS and acidic lipids sequester the lysine ubiquitylation sites within the membrane.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sarangi, S. K., Lande, K. M. & Kumar, S. KIR signaling is regulated by electrostatic interaction of its cytosolic tail with the plasma membrane despite being neutral polyampholyte. Proc. Natl Acad. Sci. USA 120, e2212987120 (2023).

Article  CAS  PubMed  Google Scholar 

Cheng, H. et al. Conformational changes in the cytoplasmic region of KIR3DL1 upon interaction with SHP-2. Structure 27, 639–650 e632 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sigalov, A. B., Aivazian, D. A., Uversky, V. N. & Stern, L. J. Lipid-binding activity of intrinsically unstructured cytoplasmic domains of multichain immune recognition receptor signaling subunits. Biochemistry 45, 15731–15739 (2006).

Article  CAS  PubMed  Google Scholar 

Moes, B. et al. INPP5K controls the dynamic structure and signaling of wild-type and mutated, leukemia-associated IL-7 receptors. Blood 141, 1708–1717 (2023).

Article  CAS  PubMed  Google Scholar 

Dong, R. et al. Molecular dynamics of the recruitment of immunoreceptor signaling module DAP12 homodimer to lipid raft boundary regulated by PIP2. J. Phys. Chem. B 124, 504–510 (2020).

Article  CAS  PubMed  Google Scholar 

Sun, F. et al. Molecular mechanism for bidirectional regulation of CD44 for lipid raft affiliation by palmitoylations and PIP2. PLoS Comput. Biol. 16, e1007777 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Araya-Secchi, R. et al. The prolactin receptor scaffolds Janus kinase 2 via co-structure formation with phosphoinositide-4,5-bisphosphate. eLife 12, e84645 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Haxholm, G. W. et al. Intrinsically disordered cytoplasmic domains of two cytokine receptors mediate conserved interactions with membranes. Biochem. J. 468, 495–506 (2015).

Article  CAS  PubMed  Google Scholar 

Paddock, C. et al. Residues within a lipid-associated segment of the PECAM-1 cytoplasmic domain are susceptible to inducible, sequential phosphorylation. Blood 117, 6012–6023 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wu, W., Shi, X. & Xu, C. Regulation of T cell signalling by membrane lipids. Nat. Rev. Immunol. 16, 690–701 (2016).

Article  CAS  PubMed  Google Scholar 

Lorent, J. H. et al. Plasma membranes are asymmetric in lipid unsaturation, packing and protein shape. Nat. Chem. Biol. 16, 644–652 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Doktorova, M., Symons, J. L. & Levental, I. Structural and functional consequences of reversible lipid asymmetry in living membranes. Nat. Chem. Biol. 16, 1321–1330 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wen, Y., Vogt, V. M. & Feigenson, G. W. PI(4,5)P2 clustering and its impact on biological functions. Annu. Rev. Biochem. 90, 681–707 (2021).

Article  CAS  PubMed  Google Scholar 

Posor, Y., Jang, W. & Haucke, V. Phosphoinositides as membrane organizers. Nat. Rev. Mol. Cell Biol. 23, 797–816 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schink, K. O., Tan, K. W. & Stenmark, H. Phosphoinositides in control of membrane dynamics. Annu. Rev. Cell Dev. Biol. 32, 143–171 (2016).

Article  CAS  PubMed