Abstract 1051: Atypical PKC and TGFβ receptors co-operate to phosphorylate Par6
Bibliographic record
Abstract
Abstract Transforming growth factor beta (TGFβ) is involved in many aspects of cellular behavior including apoptosis and differentiation. In tumor cells, TGFβ signaling alters cell plasticity through a loss in apical-basal cell polarity and induces epithelial to mesenchymal transition (EMT). Integral to this process is the phosphorylation of a polarity protein, Par6, on a conserved serine residue (S345). Recent work has shown that phosphorylation of this site not only increases cell plasticity and EMT, but also promotes an invasive phenotype in breast cancer cells. Our work suggests that a polarity partner of Par6, atypical Protein Kinase C (aPKC), can also phosphorylate Par6 on this critical site to drive distinct cellular changes in non-small cell lung cancer (NSCLC) cells. Using co-immunoprecipitation studies and immunofluorescence microscopy, we show that aPKCι interacts with TGFβ receptors through the adaptor Par6, and that these proteins localize to the leading edge of migrating cells. Furthermore, co-expression of Par6 with TGFβ receptors results in increased phospho-Par6 levels as previously reported. However, we have also found that phosphorylation of Par6 increases in the presence of aPKC. aPKC kinase activity as well as association with Par6 were found to be important for Par6 phosphorylation as evidenced by a loss in phospho-Par6 using a kinase deficient mutant of PKCζ (PKCζ -KR) as well as a mutant of Par6 that does not bind aPKC (Par6-K19A). Furthermore, gene silencing of atypical PKC reduces TGFβ induced cell morphology changes, E-cadherin loss, and stress fiber production. Finally, gene silencing of atypical PKC was observed to reduce TGFβ dependent migration of NSCLC cells. In conclusion, our results indicate that atypical PKC cooperate with TGFβ receptors to regulate phospho-Par6 levels to drive an invasive phenotype of NSCLC cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1051. doi:10.1158/1538-7445.AM2011-1051
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".