Phosphorylation of tight junction transmembrane proteins: Many sites, much to do

Abstract

Phosphorylation is a dynamic post-translational modification that can alter protein structure, localization, protein-protein interactions and stability. All of the identified tight junction transmembrane proteins can be multiply phosphorylated, but only in a few cases are the consequences of phosphorylation at specific sites well characterized. The goal of this review is to highlight some of the best understood examples of phosphorylation changes in the integral membrane tight junction proteins in the context of more general overview of the effects of phosphorylation throughout the proteome. We expect as that structural information for the tight junction proteins becomes more widely available and the molecular modeling algorithms improve, so will our understanding of the relevance of phosphorylation changes at single and multiple sites in tight junction proteins.

Keywords: JAM; claudin; occludin; phosphorylation.

Figure 1.

Selected cldn cytoplasmic domains. Red text, phosphorylation sites identified by MS; blue highlighted residues are referred to in text, purple highlight identified ubiquitination site blocked by adjacent phosphorylation. Double underline identified regions predicted to be disordered (see text).

Figure 2.

JAM-A, CAR and CLMP cytoplasmic domains. Red text, phosphorylation sites identified by MS (¹⁴; blue highlighted residues are referred to in text, double underline identified regions predicted to be disordered (see text).

Figure 3.

Ocln, tricellulin and marvelD3 cytoplasmic N- and C-terminal domains. Red text, phosphorylation sites identified by MS; blue highlighted residues are referred to in text, double underline identified regions predicted to be disordered (see text). Yellow highlighted area in ocln C-terminal domain identifies area with structural information.