PRKCI Human
Description
Cancer Research: PRKCI Amplification and Oncogenic Roles
PRKCI is frequently amplified in cancers, driving tumorigenesis through mechanisms such as immune suppression, apoptosis evasion, and polarity disruption.
Gastric Cancer
High PRKCI mRNA expression correlates with poor prognosis in gastric cancer patients:
Ovarian Cancer
PRKCI amplification is prevalent in clear cell and high-grade serous ovarian cancers (HGSOC):
Osteosarcoma
PRKCI overexpression promotes proliferation and colony formation:
| Experimental Model | Outcome | Source |
|---|---|---|
| PRKCI Overexpression | Increased CCK-8 growth rates; 2–3× higher colony counts | |
| PRKCI Knockdown | Reduced cell growth; inhibited colony formation |
Genetic Implications: PRKCI Variants in Developmental Disorders
Recent studies identify PRKCI as a causal gene for Van der Woude syndrome (VWS) and syndromic orofacial clefts (OFCs):
Key Findings:
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PRKCI variants disrupt periderm formation, critical for embryonic epithelial barrier integrity.
Therapeutic Targeting: Challenges and Opportunities
Applications in Research and Diagnostics
Product Specs
PRKCI, also known as AKAPKC iota, belongs to the serine/threonine protein kinase family and plays a crucial role in regulating various cellular processes, including hormone secretion, cell growth and differentiation, and gene expression. It is essential for cell polarization and the development of epithelial tight junctions. This kinase is calcium-independent and relies on phospholipids for its activity. PRKCI is also involved in activating multiple signaling pathways, such as Ras, NF-kappa-B, and c-Src pathways.
Recombinant human PRKCI, expressed in HEK cells, is a single, glycosylated polypeptide chain encompassing amino acids 1 to 596. With a 6-amino acid His-tag fused at the C-terminus, the protein has a total of 602 amino acids and a molecular weight of 69 kDa. The purification process involves proprietary chromatographic techniques.
The PRKCI solution is provided at a concentration of 0.5 mg/ml in a buffer consisting of 10% glycerol and Phosphate-Buffered Saline (pH 7.4).
For short-term storage (2-4 weeks), the product can be stored at 4°C. For extended storage, it is recommended to freeze the product at -20°C. Adding a carrier protein such as HSA or BSA (0.1%) is advisable for long-term storage. Repeated freezing and thawing should be avoided.
The purity of the protein is determined to be greater than 80.0% by SDS-PAGE analysis.
DXS1179E, nPKC-iota, PKCI, aPKC-lambda/iota, PRKC-lambda/iota, PRKCL, Protein kinase C iota type, Protein Kinase C iota, Atypical protein kinase C-lambda/iota, PRKCI.
HEK293 Cells.
MPTQRDSSTM SHTVAGGGSG DHSHQVRVKA YYRGDIMITH FEPSISFEGL CNEVRDMCSF DNEQLFTMKW IDEEGDPCTV SSQLELEEAF RLYELNKDSE LLIHVFPCVP ERPGMPCPGE DKSIYRRGAR RWRKLYCANG HTFQAKRFNR RAHCAICTDR IWGLGRQGYK CINCKLLVHK KCHKLVTIEC GRHSLPQEPV MPMDQSSMHS DHAQTVIPYN PSSHESLDQV GEEKEAMNTR ESGKASSSLG LQDFDLLRVI GRGSYAKVLL VRLKKTDRIY AMKVVKKELV NDDEDIDWVQ TEKHVFEQAS NHPFLVGLHS CFQTESRLFF VIEYVNGGDL MFHMQRQRKL PEEHARFYSA EISLALNYLH ERGIIYRDLK LDNVLLDSEG HIKLTDYGMC KEGLRPGDTT STFCGTPNYI APEILRGEDY GFSVDWWALG VLMFEMMAGR SPFDIVGSSD NPDQNTEDYL FQVILEKQIR IPRSLSVKAA SVLKSFLNKD PKERLGCHPQ TGFADIQGHP FFRNVDWDMM EQKQVVPPFK PNISGEFGLD NFDSQFTNEP VQLTPDDDDI VRKIDQSEFE GFEYINPLLM SAEECVHHHH HH
Q&A
Here’s a structured collection of FAQs tailored for academic researchers studying PRKCI in human biology, incorporating experimental design considerations, methodological guidance, and data analysis insights:
What are the primary functional roles of PRKCI in human cellular processes?
PRKCI encodes atypical protein kinase C iota (PKCι), which regulates:
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Autophagy in pancreatic ductal adenocarcinoma (PDAC) through mTOR signaling
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Oncogenic signaling via amplification at 3q26 in cancers (e.g., lung, ovarian, esophageal)
Methodological note: To validate these roles, use:
Which human diseases are most strongly associated with PRKCI variants?
Experimental design tip: Prioritize whole-genome sequencing (WGS) for de novo variant detection in syndromic cases .
How do PRKCI variants cause phenotypic heterogeneity in peridermopathies?
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Variant location dictates phenotype:
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Functional validation: Use zebrafish ectodermal explants to test ectopic periderm formation .
What explains contradictory data on PRKCI's role in cancer progression?
Key contradiction: circPRKCI (a circular RNA derivative) may oppose linear PRKCI transcripts in some contexts . Address this via isoform-specific silencing (siRNA vs. CRISPR).
How can researchers model PRKCI-linked peridermopathies experimentally?
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Mouse models: Conditional knockout in palatal mesenchyme replicates cleft phenotypes
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In vitro systems: 3D organoids derived from patient iPSCs to study cell polarity defects
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Functional assays:
What statistical approaches resolve low-penetrance PRKCI variants in population studies?
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Burden testing: Combine case-control cohorts with >1,000 trios to detect de novo enrichment (p=8.56×10⁻⁸ in VWS)
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Meta-analysis: Use random-effects models for circPRKCI prognostic studies (I² >50%)
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Phenotype stratification: Separate OFC cases by subtype (e.g., cleft lip vs. palate) to reduce heterogeneity
How to interpret PRKCI's moderate LOEUF score (0.66) in gnomAD?
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Implication: Tolerates some loss-of-function (LOF) variants but constrained in specific domains (e.g., PB1)
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Resolution: Perform regional constraint analysis using DECIPHER or ClinVar to identify pathogenic hotspots
Why do some PRKCI variants lack functional validation?
Product Science Overview
Protein Kinase C iota (PKCι), also known as atypical protein kinase C-lambda/iota (aPKC-λ/ι) and PRKCI, is a member of the protein kinase C (PKC) family. This family of serine/threonine kinases plays a crucial role in various cellular processes, including cell proliferation, differentiation, and apoptosis. PKCι is classified as an atypical PKC due to its unique regulatory properties and structural features.
PKCι is a cytoplasmic, membrane, and nuclear protein that belongs to the AGC (protein kinase A, G, and C) superfamily. It contains several distinct domains:
- AGC-kinase C-terminal domain
- OPR domain
- Phorbol-ester/DAG-type zinc finger
- Protein kinase domain
These domains enable PKCι to interact with various substrates and regulatory proteins, facilitating its role in multiple signaling pathways. Unlike classical PKCs, PKCι is calcium-independent and phospholipid-dependent, making it unique in its activation and function.
PKCι is involved in several critical cellular processes:
- Cell Polarization: PKCι plays a vital role in establishing and maintaining cell polarity, which is essential for proper cell function and tissue organization.
- Epithelial Tight Junctions: It contributes to the formation and maintenance of tight junctions in epithelial cells, which are crucial for barrier function and tissue integrity.
- Signaling Pathways: PKCι is implicated in the activation of several signaling pathways, including Ras, c-Src, and NF-kappa-B pathways. These pathways are involved in cell growth, survival, and differentiation.
- Apoptosis: PKCι functions in both pro- and anti-apoptotic pathways, highlighting its complex role in cell survival and death.
- Microtubule Dynamics: Through its interaction with RAB2A and GAPDH, PKCι influences microtubule dynamics and is recruited to vesicular tubular clusters (VTCs), which are essential for intracellular transport .
PKCι has been shown to play a pivotal role in cancer development and progression. Its overexpression is associated with poor prognosis in various cancers, including lung adenocarcinoma. PKCι’s involvement in the Hippo/YAP pathway, which is commonly disrupted in cancers, further underscores its significance in tumorigenesis .
Recombinant human PKCι is produced using baculovirus expression systems in Sf9 insect cells. The recombinant protein is typically tagged with a GST (glutathione S-transferase) tag to facilitate purification and detection. It is supplied in a sterile buffer solution and should be stored at –70°C to maintain stability and activity .
