I am studying the protein kinase GSK3 and I am learning about the regulation of its activity. Many journal papers that I have read have stated that GSK3 is unique because it is a constitutively active kinase, meaning that it is always active and is not activated in response to a specific stimulus/condition. I have read that phosphorylation of GSK3 at specific tyrosine residues only enhances its activity, but the GSK3 itself is always active.
However, many of these papers also talk about the various mechanisms through which the activity of GSK3 is regulated (e.g. through phosphorylation at specific amino acid residues, subcellular localisation, protein complex formation). One paper states the following:
The many functions regulated by GSK3 (through its phosphorylation of numerous substrates) suggests that the activity of GSK3 must be highly regulated. Four key mechanisms have been identified that contribute to regulating the actions of GSK3 in a substrate-specific manner. These include regulation by phosphorylation of GSK3 itself, the subcellular localization of GSK3, the formation of protein complexes containing GSK3, and the phosphorylation state of GSK3 substrates.
I am wondering how is it possible for a kinase to be constitutively active and be highly regulated at the same time? If it is constitutively active, doesn't this imply that it is always active? Any insights are appreciated.