Editors' ChoiceDevelopment

Kinase-Independent Functions for FRK-1

STKE  05 Jul 2005:
Vol. 2005, Issue 291, pp. tw244
DOI: 10.1126/stke.2912005tw244

Putzke et al. report the identification and characterization of Fer-related kinase 1 (FRK-1) in Caenorhabditis elegans. FRK-1 is most similar to a truncated form of Fer (FerT) that lacks a coiled-coil region. The greatest similarity between mammalian Fer and FRK-1 lies in the SH2 domain and a tyrosine kinase domain. The kinase activity of FRK-1 was confirmed by its ability to autophosphorylate. Worms lacking FRK-1 (either through RNAi or through genomic deletion) showed defective epidermal enclosure and differentiation. Expression of frk-1 in seam cells of the epidermis rescued the morphogenic defects. The kinase domain was not necessary for FRK-1 to rescue the epidermal enclosure phenotype, because a kinase-inactive mutant version of FRK-1 (D308R) was effective in rescue assays. The localization of FRK-1 was dynamic and varied with mitotic activity. In dividing cells, FRK-1 was found in the nucleus and at points of cell-cell contact. During periods of mitotic inactivity, such as just before epidermal enclosure, FRK-1 is detectable only in the cytoplasm and at the plasma membrane. However, FRK-1 localization at the plasma membrane was disrupted in worms lacking β-catenin (HMP-2 in C. elegans) or p120 catenin (JAC-1 in C. elegans) or β-integrin (PAT-3, which is expressed in the body wall muscle and not the epidermis), which suggests that an interaction with adhesion complexes and possibly communication from the body wall muscles to the epidermis controls FRK-1 localization. Because worms with these genetic backgrounds did not show disrupted epidermal enclosure phenotypes, it remains unclear exactly how the interaction with cell adhesion complexes contributes to the morphogenic functions of FRK-1.

A. P. Putzke, S. T. Hikita, D. O. Clegg, J. H. Rothman, Essential kinase-independent role of a Fer-like non-receptor tyrosine kinase in Caenorhabditis elegans morphogenesis. Development 132, 3185-3195 (2005). [Abstract] [Full Text]