Oncogenic B-Raf proto-oncogene, serine/threonine kinase-mediated hedgehog signalling in the pathogenesis and targeted therapy of melanoma

Table 1 Protein kinases involved in the regulation of hedgehog pathway

Protein kinases	Effect on HH signaling	Ref.
Protein kinase A	Inhibits GLI1, GLI2, GLI3	[87]
	Activates SMO
	Stabilizes SUFU
Casein kinase 1	Activates/inhibits GLI	[88]
	Activates SMO
Casein kinase 2	Activates GLI1, GLI2	[89,90]
Glycogen synthase kinase 3β	Inhibits GLI2, GLI3	[15]
	Stabilizes SUFU
G protein-coupled receptor kinase 2	Stabilizes and activates SMO	[91]
Dual-specificity tyrosine phosphorylation-regulated kinase 1A and Dual-specificity tyrosine phosphorylation-regulated kinase 1B	Activates/inhibits GLI	[92]
Dual-specificity tyrosine phosphorylation-regulated kinase 2	Inhibits GLI2	[93]
Extracellular signal-regulated kinases 1/2	Activates HH signaling	[94,95]
Protein kinase B	Activates HH signaling	[96]
Ribosomal protein S6 kinase 1	Activates GLI1	[97,98]
Protein kinase C α, δ	Activates/inhibits GLI1	[99,100]
Atypical protein kinase Cι/λ	Activates GLI1	[101]
5’ adenosine monophosphate-activated protein kinase	Inhibits/activates HH signaling	[102,103]
Unc-51 Like kinase 3	Activates/inhibits GLI	[104]
Serine/threonine-protein kinase	Activates HH signaling	[105]
Integrin-linked kinase	Activates HH signaling	[106]
RIO kinase 3	Activates HH signaling	[107]
Never in mitosis gene A-related kinase 2	Increases SUFU stability repressing GLI2	[108,109]
Liver kinase B1	Inhibits HH signaling	[110]
Polo-like kinase 1	Inhibits GLI1	[111]
Mitogen-activated protein kinase kinase kinase 1	Inhibits GLI1	[112]
Mitogen-activated protein kinase kinase kinase 2/3	Enhances GLI1-SUFU association	[113]
Mitogen-activated protein kinase kinase kinase 10	Activates GLI1 and GLI2	[114]
C-Jun N-terminal kinase	Activates GLI2 and GLI3	[115,116]

GLI: Glioma-associated oncogene homolog; SMO: Smoothened; SUFU: Suppressor of fused; HH: Hedgehog.