Continuing to stretch the bounds of what the extracellular matrix is known to do, Swindle et al. (page 459) show that tenascin-C, a matrix protein, can signal through the epidermal growth factor receptor (EGFR). The authors suggest that the distinction between receptor interactions that lead to signaling and those that anchor the cell in the environment may be far more tenuous than commonly thought.
Figure .
Tenascin-covered beads bind cells (top) unless an antibody to EGFR is present (bottom).
Tenascin-C is found in the surrounding matrix when cells are actively dividing and moving: for example, during embryonic development, wound healing, and in invasive cancers. These are also occasions when EGFR is known to be activated. Its previously known ligands are soluble proteins. The study used cells that lack endogenous EGFR ligands to show that tenascin-C, and specifically its EGF-like repeats, activate EGFR in a dose-dependent way. Further, the study shows that EGFR and tenascin-C bind to each other directly.
Although the affinity between tenascin-C and EGFR is relatively low, the fact that tenascin-C is tethered increases its effective concentration, and because it is not internalized and degraded like soluble ligands, signaling is not attenuated. The authors conjecture that cells use soluble ligands for shorter, finely timed responses and tethered ligands for persistent signaling in defined regions. ▪