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Proteomic and Phosphoproteomic Profiling Reveals the Oncogenic Role of Protein Kinase D Family Kinases in Cholangiocarcinoma

Cholangiocarcinoma (CCA) is a lethal malignancy in the hepatobiliary system, with dysregulated protein expression and phosphorylation signaling. However, the protein and phosphorylation signatures of CCAs are little-known. Here, we performed the proteomic and phosphoproteomic profiling of tumors and normal adjacent tissues (NATs) from patients with CCA and predicted eleven PKs high-potentially related to CCA with a comprehensive inference of the functional protein kinases (PKs) (CifPK) pipeline. Besides the two known CCA-associated PKs, we screened the remaining candidates and uncovered five PKs as novel regulators in CCA. Specifically, the protein kinase D (PKD) family members, including PRKD1, PRKD2, and PRKD3, were identified as critical regulators in CCA. Moreover, the pan-inhibitor of the PKD family, 1-naphthyl PP1 (1-NA-PP1), was validated as a potent agent for inhibiting the proliferation, migration, and invasion ability of CCA cells. This study reveals new PKs associated with CCA and suggests PRKD kinases as novel treatment targets for CCA.

 

Comments:

It sounds like the research you're referencing delves into the protein and phosphorylation patterns within cholangiocarcinoma (CCA) and identifies potential targets for treatment. The identification of novel protein kinases like PRKD1, PRKD2, and PRKD3 and their association with CCA could be significant for understanding the disease and developing targeted therapies.

The study's findings regarding the role of the PKD family members in CCA and the validation of 1-naphthyl PP1 as an inhibitor to hinder CCA cell proliferation, migration, and invasion highlight promising avenues for therapeutic intervention. This information could pave the way for the development of new treatments that specifically target these protein kinases, potentially offering more effective and tailored approaches to managing CCA.

Research like this contributes greatly to our understanding of the molecular mechanisms underlying diseases like CCA and helps in identifying potential therapeutic strategies. Exciting times for advancements in targeted therapies!

Related Products

Cat.No. Product Name Information
S2642 1-Naphthyl PP1(1-NA-PP1) 1-Naphthyl PP1(1-NA-PP 1) is a highly selective and potent pan-PKD inhibitor with IC50 of 154.6 nM,133.4 nM and 109.4 nM for PKD1, PKD2 and PKD3, respectively. 1-Naphthyl PP1 is a selective inhibitor of Src family kinases (v-Src, c-Fyn) and the tyrosine kinase c-Abl with IC50 of 1.0 μM, 0.6 μM, 0.6 μM, 18 μM and 22 μM for v-Src, c-Fyn, c-Abl, CDK2 and CAMK II, respectively.

Related Targets

Bcr-Abl PKD Src CaMK CDK