Fig. 1

The diagram structure of SIKs and related kinases. a The structure and phosphorylation residues are illustrated. SIKs are composed of KD (kinase domain) containing an LKB1 phosphorylation site, SNH domain containing UBA (ubiquitin-associated) domain and C-terminal domain containing multiple PKA phosphorylation sites. b The structure of AMPK-related family kinases are illustrated. These kinases share a similar structure with SIKs. AMPKα subunits are composed of KD, AID (autoinhibitory domain), α-linker containing two α-RIM (regulatory subunit-interacting motif) and α-CTD (C-terminal domain). SADs are composed of KD, UBA domain, and KA1 (kinase-associated domain 1), it is N-terminal next to the AIS sequence (autoinhibitory sequence). MARKs are composed of KD, UBA domain, spacer, and tail domain (including the KA1 domain). NUAKs are composed of KD and UBA domain. SNRK is composed of KD and UBA domain. The phosphorylation sites on the T-loop of AMPK-related family kinases are illustrated. The AMPK-related family kinases can be directly phosphorylated and activated by LKB1 on their T-loop (right panel). c SIK and AMPK downstream substrate phosphorylations are illustrated. SIKs phosphorylated LX(R/K/H)(S/T)XSXXXL motif (underlined, phosphorylated residue, X, any residue) and the identified AMPK substrates phosphorylation sites reside in the known AMPK phosphorylation consensus sequence (L/M/I)X(R/K/H)XXSXXX(L/V/I/F) are illustrated