Cytoskeleton-Associated Protein 4: Functions Beyond the Endoplasmic Reticulum in Physiology and Disease

Figure 3

Model of CKAP4’s functions at the plasma membrane, ER, and nucleus. (a) CKAP4 has been determined to able to bind the ER to microtubules and is suspected of stabilizing the ER and/or stabilizing microtubules [6]. (b) The palmitoylation of CKAP4 by DHHC2 has been shown to be required for APF mediated signaling [14, 22]. (c) The binding of SP-A to CKAP4 inhibits the secretion of surfactant [12]. (d) An interaction between cAMP and Epac causes a signal cascade stimulating PI3-Kinase which in turn activates Akt and increases the transport of CKAP4 from the ER to the plasma membrane [18]. (e) The SP-A/CKAP4 interaction is recycled via a clathrin pathway and is stimulated by the cAMP signaling cascade [18]. (f) CKAP4 binds to the CCN2 promoter via its C-terminal domain (residues 126–501 which includes the bZIP-like DNA-binding domain) in an APF-dependent fashion [13]. It is not known whether APF binds CKAP4 in the nucleus.