Unique Intracellular Trafficking Processes Associated With Neural Cell Adhesion Molecule and Its Intracellular Signaling

Abstract

Homophilic binding of the neural cell adhesion molecule (NCAM) results in intracellular signaling, which also involves heterophilic engagement of coreceptors such as the fi broblast growth factor receptor (FGFR) and receptor protein tyrosine phosphatase-α (RPTP α ). NCAM ' s own cellular dynamic itinerary includes endocytosis and recycling to the plasma membrane. Recent works suggest that NCAM could infl uence the traffi cking of other receptor molecules that it associates with, particularly the FGFR. Furthermore, it was demonstrated that NCAM could undergo proteolytic processing upon activation. A processed fragment of NCAM, together with an N-terminal fragment of focal adhesion kinase (FAK), is translocated into the nucleus. Here, the authors discuss these rather unique (though not without precedence and analogues) receptor traffi cking activities that are associated with NCAM and NCAM signaling.

All Good Things Must End: Termination of Receptor Tyrosine Kinase Signal

“…Their function is based on their ability to bind extracellular ligands and to form dimers or oligomers that show active intracellular kinase domains and determine receptor phosphorylation. In fact, the contact between the KDs of dimers stimulates catalytic activity, SHC, SRC, phospholipase Cγ, STAT1, Gab1, and FRS2α are recruited after tion of the docking sites, and the Ras-Raf-Erk 1/2 and the PI3K-Akt pathway [6]. Intriguingly, individual RTKs can bind several ligands that can induce d dimerization of the receptor [1].…”