Serum and glucocorticoid-regulated protein kinases: variations on a theme.
The phosphatidylinositol 3' kinase (PI3K)-signaling pathway plays a critical role in a variety of cellular responses such as modulation of cell survival, glucose homeostasis, cell division, and cell growth. PI3K generates important lipid second messengers-phosphatidylinositides that are phosphorylated at the 3' position of their inositol ring head-group. These membrane restricted lipids act by binding with high affinity to specific protein domains such as the pleckstrin homology (PH) domain. Effectors of PI3K include molecules that harbor such domains such as phosphoinositide-dependent kinase (PDK1) and protein kinase B (PKB), also termed Akt. The mammalian genome encodes three different PKB genes (alpha, beta, and gamma; Akt1, 2, and 3, respectively) and each is an attractive target for therapeutic intervention in diseases such as glioblastoma and breast cancer. A second family of three protein kinases, termed serum and glucocorticoid-regulated protein kinases (SGKs), is structurally related to the PKB family including regulation by PI3K but lack a PH domain. However, in addition to PH domains, a second class of 3' phosphorylated inositol phospholipid-binding domains exists that is termed Phox homology (PX) domain: this domain is found in one of the SGKs (SGK3). Here, we summarize knowledge of the three SGK isoforms and compare and contrast them to PKB with respect to their possible importance in cellular regulation and potential as therapeutic targets.
Tessier
Maude
M
Department of Medical Biophysics, Samuel Lunenfeld Research Institute, University of Toronto, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.
Woodgett
James R
JR
D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D004249:DNA Damage; D005786:Gene Expression Regulation; D007473:Ion Channels; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction
D007473:Ion Channels; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases