Gli Phosphorylation Code in Hedgehog Signal Transduction.

Front Cell Dev Biol

Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, United States.

Published: January 2022

Hedgehog (Hh) family of secreted proteins governs many key processes in embryonic development and adult tissue homeostasis in species ranging from insects to human. Deregulation of Hh signaling has been implicated in a wide range of human diseases including birth defect and cancer. Hh signaling pathway culminates in the conversion of the latent transcription factor Cubitus interruptus (Ci)/Gli from a repressor form (Ci/Gli) into an activator form (Ci/Gli). Both the production of Ci/Gli in the absence of Hh and the formation of Ci/Gli in response to Hh are regulated by phosphorylation. Whereas previous studies demonstrated that sequential phosphorylation by protein kinase A (PKA), glycogen synthase kinase 3 (GSK3), and casein kinase 1 (CK1) at multiple Ser/Thr clusters in the C-terminal region of Ci/Gli targets it for proteolytic processing to generate Ci/Gli, recent studies revealed that phosphorylation of Ci/Gli by the Fused (Fu)/Unc-51 like kinase (Ulk) family kinases Fu/Ulk3/Stk36 and other kinases contributes to Ci/Gli activation. Fu/Ulk3/Stk36-mediated phosphorylation of Ci/Gli is stimulated by Hh, leading to altered interaction between Ci/Gli and the Hh pathway repressor Sufu. Here we review our current understanding of how various Ci/Gli phosphorylation events are regulated and how they influence Hh signal transduction.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855225PMC
http://dx.doi.org/10.3389/fcell.2022.846927DOI Listing

Publication Analysis

Top Keywords

ci/gli
12
signal transduction
8
form ci/gli
8
phosphorylation ci/gli
8
phosphorylation
5
gli phosphorylation
4
phosphorylation code
4
code hedgehog
4
hedgehog signal
4
transduction hedgehog
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!