Cellular and Molecular Life Sciences

, Volume 75, Issue 8, pp 1393–1409 | Cite as

Junctional adhesion molecule-A: functional diversity through molecular promiscuity

  • Tim Steinbacher
  • Daniel Kummer
  • Klaus Ebnet


Cell adhesion molecules (CAMs) of the immunoglobulin superfamily (IgSF) regulate important processes such as cell proliferation, differentiation and morphogenesis. This activity is primarily due to their ability to initiate intracellular signaling cascades at cell–cell contact sites. Junctional adhesion molecule-A (JAM-A) is an IgSF-CAM with a short cytoplasmic tail that has no catalytic activity. Nevertheless, JAM-A is involved in a variety of biological processes. The functional diversity of JAM-A resides to a large part in a C-terminal PDZ domain binding motif which directly interacts with nine different PDZ domain-containing proteins. The molecular promiscuity of its PDZ domain motif allows JAM-A to recruit protein scaffolds to specific sites of cell–cell adhesion and to assemble signaling complexes at those sites. Here, we review the molecular characteristics of JAM-A, including its dimerization, its interaction with scaffolding proteins, and the phosphorylation of its cytoplasmic domain, and we describe how these characteristics translate into diverse biological activities.


Cell adhesion Dimerization JAM-A Junctional adhesion molecules PDZ domain Scaffolding protein Signaling 



Amino acid


Adherens junctions


Atypical protein kinase C




Coxsackie and adenovirus receptor


Calcium/calmodulin-dependent serine protein kinase


Cell division cycle 42


C-Src kinase


Epithelial-to-mesenchymal transition


4.1 protein and ERM


Guanine nucleotide exchange factor


Immunoglobulin superfamily


Junctional adhesion molecule


Lethal(2) giant larvae protein homolog


Abnormal cell lineage protein


Mitogen-activated protein kinase


Multiple PDZ domain protein 1


Primordial, spot-like adherens junctions


Protein associated with Lin-7


Partitioning defective


Pals1-associated tight junction protein


Protein interacting with C kinase 1


Plasma membrane calcium-transporting ATPase 4


PSD95–Discs large–ZO-1


Ras-related C3 botulinum toxin substrate 1


Rap guanine nucleotide exchange factor


Src homology




Tight junctions


Zonula occludens



We wish to thank Volker Gerke for continuous support. This work is supported by grants from the German Research Foundation to K.E. (EB 160/4-2, EB 160/5-1, EXC-1003 FF-2016-01) and from the Medical Faculty of the University Münster to K.E. (IZKF Eb2/020/14).

Compliance with ethical standards

Conflict of interest

The authors declare to have no conflict of interest.


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Institute-Associated Research Group: Cell Adhesion and Cell Polarity, Institute of Medical Biochemistry, ZMBEUniversity of MünsterMünsterGermany
  2. 2.Cells-In-Motion Cluster of Excellence (EXC1003-CiM)University of MünsterMünsterGermany
  3. 3.Interdisciplinary Clinical Research Center (IZKF)University of MünsterMünsterGermany

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