CG-NAP/Kinase Interactions Fine-Tune T Cell Functions

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2019 Nov 30

PMID 31781123

Citations 3

Authors

Navin Kumar Verma

Madhavi Latha Somaraju Chalasani

John D Scott

Dermot Kelleher

Affiliations

Soon will be listed here.

Abstract

CG-NAP, also known as AKAP450, is an anchoring/adaptor protein that streamlines signal transduction in various cell types by localizing signaling proteins and enzymes with their substrates. Great efforts are being devoted to elucidating functional roles of this protein and associated macromolecular signaling complex. Increasing understanding of pathways involved in regulating T lymphocytes suggests that CG-NAP can facilitate dynamic interactions between kinases and their substrates and thus fine-tune T cell motility and effector functions. As a result, new binding partners of CG-NAP are continually being uncovered. Here, we review recent advances in CG-NAP research, focusing on its interactions with kinases in T cells with an emphasis on the possible role of this anchoring protein as a target for therapeutic intervention in immune-mediated diseases.

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References

Choudhuri K, Llodra J, Roth E, Tsai J, Gordo S, Wucherpfennig K . Polarized release of T-cell-receptor-enriched microvesicles at the immunological synapse. Nature. 2014; 507(7490):118-23. PMC: 3949170. DOI: 10.1038/nature12951. View

Pawson T . Specificity in signal transduction: from phosphotyrosine-SH2 domain interactions to complex cellular systems. Cell. 2004; 116(2):191-203. DOI: 10.1016/s0092-8674(03)01077-8. View

Williams R . Cutting edge: A-kinase anchor proteins are involved in maintaining resting T cells in an inactive state. J Immunol. 2002; 168(11):5392-6. DOI: 10.4049/jimmunol.168.11.5392. View

Pfeifhofer-Obermair C, Thuille N, Baier G . Involvement of distinct PKC gene products in T cell functions. Front Immunol. 2012; 3:220. PMC: 3412260. DOI: 10.3389/fimmu.2012.00220. View

Li S, Wang H, Peng B, Zhang M, Zhang D, Hou S . Efalizumab binding to the LFA-1 alphaL I domain blocks ICAM-1 binding via steric hindrance. Proc Natl Acad Sci U S A. 2009; 106(11):4349-54. PMC: 2657446. DOI: 10.1073/pnas.0810844106. View

Li G, Qian H . Sensitivity and specificity amplification in signal transduction. Cell Biochem Biophys. 2003; 39(1):45-59. DOI: 10.1385/CBB:39:1:45. View

Arumugham V, Baldari C . cAMP: a multifaceted modulator of immune synapse assembly and T cell activation. J Leukoc Biol. 2017; 101(6):1301-1316. DOI: 10.1189/jlb.2RU1116-474R. View

Wong W, Scott J . AKAP signalling complexes: focal points in space and time. Nat Rev Mol Cell Biol. 2004; 5(12):959-70. DOI: 10.1038/nrm1527. View

Sun Z, Arendt C, Ellmeier W, Schaeffer E, Sunshine M, Gandhi L . PKC-theta is required for TCR-induced NF-kappaB activation in mature but not immature T lymphocytes. Nature. 2000; 404(6776):402-7. DOI: 10.1038/35006090. View

10.

Ramstad C, Sundvold V, Johansen H, Lea T . cAMP-dependent protein kinase (PKA) inhibits T cell activation by phosphorylating ser-43 of raf-1 in the MAPK/ERK pathway. Cell Signal. 2000; 12(8):557-63. DOI: 10.1016/s0898-6568(00)00097-8. View

11.

Grader-Beck T, van Puijenbroek A, Nadler L, Boussiotis V . cAMP inhibits both Ras and Rap1 activation in primary human T lymphocytes, but only Ras inhibition correlates with blockade of cell cycle progression. Blood. 2002; 101(3):998-1006. DOI: 10.1182/blood-2002-06-1665. View

12.

Wehbi V, Tasken K . Molecular Mechanisms for cAMP-Mediated Immunoregulation in T cells - Role of Anchored Protein Kinase A Signaling Units. Front Immunol. 2016; 7:222. PMC: 4896925. DOI: 10.3389/fimmu.2016.00222. View

13.

Kortum R, Samelson L . Priming the pump: adhesion enhances T cell antigen receptor-induced signaling. Immunity. 2009; 30(1):3-5. PMC: 6684054. DOI: 10.1016/j.immuni.2008.12.007. View

14.

Fuller C, Braciale V, Samelson L . All roads lead to actin: the intimate relationship between TCR signaling and the cytoskeleton. Immunol Rev. 2003; 191:220-36. DOI: 10.1034/j.1600-065x.2003.00004.x. View

15.

Newlon M, Roy M, Morikis D, Carr D, Westphal R, Scott J . A novel mechanism of PKA anchoring revealed by solution structures of anchoring complexes. EMBO J. 2001; 20(7):1651-62. PMC: 145475. DOI: 10.1093/emboj/20.7.1651. View

16.

Larocca M, Shanks R, Tian L, Nelson D, Stewart D, Goldenring J . AKAP350 interaction with cdc42 interacting protein 4 at the Golgi apparatus. Mol Biol Cell. 2004; 15(6):2771-81. PMC: 420101. DOI: 10.1091/mbc.e03-10-0757. View

17.

Yi J, Wu X, Chung A, Chen J, Kapoor T, Hammer J . Centrosome repositioning in T cells is biphasic and driven by microtubule end-on capture-shrinkage. J Cell Biol. 2013; 202(5):779-92. PMC: 3760611. DOI: 10.1083/jcb.201301004. View

18.

Rivero S, Cardenas J, Bornens M, Rios R . Microtubule nucleation at the cis-side of the Golgi apparatus requires AKAP450 and GM130. EMBO J. 2009; 28(8):1016-28. PMC: 2683699. DOI: 10.1038/emboj.2009.47. View

19.

Mosenden R, Tasken K . Cyclic AMP-mediated immune regulation--overview of mechanisms of action in T cells. Cell Signal. 2010; 23(6):1009-16. DOI: 10.1016/j.cellsig.2010.11.018. View

20.

Wu J, de Heus C, Liu Q, Bouchet B, Noordstra I, Jiang K . Molecular Pathway of Microtubule Organization at the Golgi Apparatus. Dev Cell. 2016; 39(1):44-60. DOI: 10.1016/j.devcel.2016.08.009. View