Mouse ULK2, a novel member of the UNC-51-like protein kinases: unique features of functional domains

The UNC-51 serine/threonine kinase of C. elegans plays an essential role in axonal elongation, and unc-51 mutants exhibit uncoordinated movements. We have previously identified mouse and human cDNAs encoding UNC-51-like kinas e (ULK1), Here we report the identification and characterization of the sec ond murine member of this kinase family, ULK2, Mouse ULK2 cDNA encodes a pu tative polypeptide of 1033 aa which has an overall 52% and 33% amino acid i dentity to ULK1 and UNC-51, respectively. ULKs and UNC-51 share a typical d omain structure of an amino-terminal kinase domain, a central proline/serin e rich (PS) domain, and a carboxy-terminal (C) domain. Northern blot analys is showed that ULK2 mRNA is widely expressed in adult tissues. In situ hybr idization analysis indicated that ULK2 mRNA is ubiquitously localized in pr emature as well as mature neurons in developing nervous system. ULK2 gene w as mapped to mouse chromosome 11B1.3 and rat chromosome 10q23 by FISH. HA-t agged ULK2 expressed in COS7 cells had an apparent molecular size of simila r to 150 kDa and was autophosphorylated in vitro. Truncation mutants sugges ted that the autophosphorylation occurs in the PS domain. Although expressi on of ULK2 failed to rescue unc-51 mutant of C. elegans, a series of ULK2/U NC-51 chimeric kinases revealed that function of the kinase and PS domains are conserved among species, while the C domain acts in a species-specific manner. These results suggest that ULK2 is involved in a previously unchara cterized signaling pathway in mammalian cells.