Open AccessTyrosine phosphorylation and proteolytic cleavage of Notch are required for non-canonical Notch/Abl signaling inDrosophilaaxon guidance
Author(s) -
R. Kannan,
Eric Cox,
Lei Wang,
Irina Kuzina,
Qun Gu,
Edward Giniger
Publication year - 2017
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.15
H-Index - 36
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.151548
Subject(s) - notch signaling pathway , biology , microbiology and biotechnology , tyrosine , tyrosine phosphorylation , hes3 signaling axis , phosphorylation , notch proteins , axon , proto oncogene tyrosine protein kinase src , signal transduction , axon guidance , tyrosine kinase , biochemistry
Notch signaling is required for the development and physiology of nearly every tissue in metazoans. Much of Notch signaling is mediated by transcriptional regulation of downstream target genes, but Notch controls axon patterning in Drosophila by local modulation of Abl tyrosine kinase signaling, via direct interactions with the Abl cofactors Disabled and Trio. Here we show that Notch-Abl axonal signaling requires both of the proteolytic cleavage events that initiate canonical Notch signaling. We further show that some Notch protein is tyrosine-phosphorylated in Drosophila, that this population of tyrosine-phosphorylated Notch is selectively associated with Disabled and Trio, and that relevant tyrosines are essential for Notch-dependent axon patterning but not for canonical Notch-dependent regulation of cell fate. Based on these data, we propose a model for the molecular mechanism by which Notch controls Abl signaling in Drosophila axons.