Role of the Phox Homology Domain and Phosphorylation in Activation of Serum and Glucocorticoid-regulated Kinase-3
Bibliographic record
Abstract
Serum and glucocorticoid-regulated kinases (SGKs) form a family of serine/threonine protein kinases that exhibit structural and sequence similarity to the protein kinase B (PKB)/Akt family. The major difference between these two families is the absence of a lipid-binding, pleckstrin homology domain in the SGKs. Despite the absence of the pleckstrin homology domain, activation of the three human isoforms is, like PKB, dependent upon the phosphatidylinositol 3'-kinase (PI3K) pathway that is induced by growth factors and mitogens. Full-length SGK3 contains a complete Phox homology (PX) domain that targets the protein to endosomes. Both a functional PX domain and PI3K activation are necessary for phosphorylation of SGK3 at two regulatory sites (Thr-320 and Ser-486) and subsequent induction of kinase activity. PDK1 phosphorylates endosome-associated SGK3 at Thr-320, whereas diversion of SGK3 to the plasma membrane, where PDK1 normally activates PKB, interferes with PDK1 phosphorylation of SGK3. A chimeric protein in which the carboxyl-terminal hydrophobic motif (HM) of SGK3 has been exchanged for the HM of PRK2 is constitutively active. Finally, we demonstrate that SGK3 activation becomes PX domain-independent once the HM is phosphorylated. Taken together, these data indicate that the targeting of SGK3 to endosomes, mediated by its PX domain, is essential for proper SGK3 activation, likely due to co-localization of SGK3 with an endosomal, PI3K-dependent and staurosporine-sensitive HM kinase.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".