Revelations of the RYK receptor

Significant progress has been made over the last decade in elucidating the mechanisms employed by receptor protein tyrosine kinases (RTKs) in transduc ing extracellular signals critical for the regulation of diverse cellular a ctivities. Nevertheless, revealing the biological significance of a subset of the RTKs that contain catalytically inactive protein tyrosine kinase dom ains has proven more elusive. ErbB3 has served as the prototype for models of catalytically inactive RTK function, performing the role of signal diver sification in heterodimeric receptor complexes with other ErbB subfamily me mbers. The receptor related to tyrosine kinases (RYK) is unique amongst the catalytically inactive RTKs. Based on structural or functional properties of the extracellular domain, RYK cannot be classified into an existing RTK subfamily. Recent genetic analyses of mouse Ryk and its Drosophila ortholog ue derailed have defined a role for this novel subfamily of receptors in th e control of craniofacial development and neuronal pathway selection, respe ctively. Recent biochemical data lead us to propose a model that involves R YK in signal crosstalk and scaffold assembly with Eph receptors. This model is consistent with the established roles of Eph receptors and ephrins in c raniofacial and nervous system morphogenesis. (C) 2001 John Wiley & Sons, I nc.