Kinase Family PIK
Kinase Classification: Group PKL: Family PIK
Related to PIKK, these phosphorylate phosphatidyl inositol on the 3' and 4' positions (PI3K, PI4K), and some have autokinase activity.
Subfamilies
There are six major subfamilies:
PI3K1 includes human genes PIK3CA (p110a), PIK3CB (p110b), PIK3CG (p110g) and PIK3CD (p110 delta)
PI3K2 includes human genes PIK3C2A, PIK3C2B, and PIK3C2G
PI3K3 includes the human PIK3C3 and yeast vps34.
PI4KA includes human PI4KA
PI4KB includes human PI4KB
PI4K2 is a highly divergent subfamily of PIK and includes human PI4K2A and PI4K2B
Domain Structure
Evolution
Protein Kinase Activity=
Several reports indicate that multiple PIKs have autokinase (autophosphorylation) activity. Yeast Vps34 (PI3K3) was shown to autophosphorylate on serine [1]. Human PI3Kgamma (which one is that?) [2]
Stoyanov et al., 1995; Bondeva et al., 1998; Bondev et al., 1999
~110 has an associated Mn2+-dependent protein kinase activity that can phosphorylate a specific serine, Ser-608, in the ~85 subunit, resulting in inhibition of PI 3-kinase activity (Car- penter et al., 1993; Dhand et al., 1994). Mutation of Arg- 916 in motif I in the PI 3-kinase domain not only eliminates PI 3-kinase activity but also abolishes the protein-serine kinase activity, establishing that this activity is intrinsic (Dhand et al., 1994). This phosphotransfer usually occurs within the ~1101~85 heterodimer (Dhand et al., 1994) but under some conditions, phosphorylation of exogenous
References
- Stack JH and Emr SD. Vps34p required for yeast vacuolar protein sorting is a multiple specificity kinase that exhibits both protein kinase and phosphatidylinositol-specific PI 3-kinase activities. J Biol Chem. 1994 Dec 16;269(50):31552-62.
- Stoyanova S, Bulgarelli-Leva G, Kirsch C, Hanck T, Klinger R, Wetzker R, and Wymann MP. Lipid kinase and protein kinase activities of G-protein-coupled phosphoinositide 3-kinase gamma: structure-activity analysis and interactions with wortmannin. Biochem J. 1997 Jun 1;324 ( Pt 2)(Pt 2):489-95. DOI:10.1042/bj3240489 |
