Fig. 5

Functional interactions of band 4.1/JEF domains with transmembrane proteins. The interactions of four well-studied examples of proteins containing band 4.1/JEF domain with transmembrane proteins are schematized. (A) In erythrocytes band 4.1 binds to the cytoplasmic tail of glycophorin C and with a specific sequence of p55, a protein that also contains PDZ and SH3 domains. The PDZ domain of p55 binds to the C terminus of glycophorin C, forming a ternary complex. Other partners of band 4.1 include actin, spectrin, and band 3. (B) ERM proteins are thought to be in a closed state and, following activation, to bind to the cytoplasmic tail of several transmembrane proteins (CD44, CD43, ICAM-2, ICAM-3). This activating step may involve binding to phosphatidylinositol 4,5-bisphosphate (PIP2) and action of Rho-GTP and/or a protein kinase. ERM proteins also interact with EBP-50/NHE-RF, a protein with two PDZ domains associated with Na⁺/H⁺ exchanger, and with (C) FAK is in the cytoplasm in an inactive state. Following integrin engagement, it is targeted to the focal adhesions by a C-terminal sequence (FAT, focal adhesion targeting) that interacts with an unidentified target (T) and multiple other proteins. The band 4.1/JEF domain interacts with the cytoplasmic tail of β integrins, and this may participate in the activation of FAK. Although for the sake of simplicity the autophosphorylation of FAK is shown as an intramolecular reaction, it may be intermolecular. (D) The JAK kinases interact with the membrane-proximal region of cytokine receptors (only one chain is shown), through their N-terminal band 4.1/JEF domain. Activation of the kinase requires additional steps triggered by cytokine binding to the receptor (not shown). GUK, guanylate kinase domain; TK; tyrosine kinase domain; KL, kinase-like domain. Question marks (?) indicate the likely existence of proteic partners, yet to be identified.