Kinase Cell Lines
Membrane protein stable cell lines are widely used in many areas of biomedical research. Creative Biolabs can offer membrane protein stable cell lines to stablish in vitro models for High Throughput Screening.
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Background of Protein Kinase
Protein kinases covalently modify other proteins mainly by phosphorylation and are widely distributed in the human body. They are mostly serine/threonine and tyrosine-specific kinases in addition to some other types of kinases in small amounts. In various organisms, the catalytic subunit domains of protein kinases are highly conserved. It consists of an N-terminus and a C-terminus domain, and the C-terminus contains two subordinate ring structures, which are identified as activation and catalytic loops, respectively. The structures of approximately 300 human protein kinases have been verified, and most of them conform to this pattern.
Fig.1 Structure Prediction of human phosphoinositide 3-kinase regulatory subunit 6.1
Functions and Mechanisms of Protein Kinase
The function of protein kinases is initiated by chemical molecule signaling or specific cellular events such as DNA damage, cAMP, Ca2+, etc. In addition, some protein kinases can also be directly activated by binding to their ligands. After initiation, protein kinases add phosphate groups to proteins and modify them through a process called phosphorylation. This kind of kinases can modify up to 30% of human proteins, therefore involved in a wide variety of activities and functions cellularly. They also participate in the majority of cellular pathways, especially those that require signal transduction.
Applications and Pathology of Kinase Cell Lines
Disruption, destruction, overexpression, or knockout of kinase genes can lead to a majority of serious diseases, including diabetes, neurological disorders, or cancer. It can also cause metabolic disorders, behavioral disorders, or death at the cellular level. In addition to this, the catalytic subunits of protein kinases are highly conserved, leading to large screens to develop kinase-specific inhibitors for the treatment of various diseases.
Published Data
| Paper Title | Protein kinase A distribution in meningioma |
| Journal | Cancers |
| Published | 2019 |
| Abstract | Dysregulation of signaling mechanisms can be detected in almost every type of tumor cell, including abnormal cytoskeletal signaling observed in meningiomas. Tumor suppressor proteins extensively interact with multiple signaling pathways, including the widely studied cyclic adenosine monophosphate (cAMP) pathway. PKA contains two regulatory factors and two catalytic subunits. After the cAMP molecule binds to the regulatory factors, PKA is responsible for phosphorylating and releasing the target protein subunits, thereby activating the cAMP signaling cascade. In previous studies, the differential distribution of PKA in tumor cells has been detected in glioblastoma and medulloblastoma, but similar studies for meningioma are still absent. To extend similar conclusions to meningiomas and explore viable tumor markers, the researchers examined the distribution of PKA and its catalytic subunits in tissue samples from meningioma patients. Observation results suggest the possibility of using the PKA molecule and its associated intracellular pathways as a diagnostic tool for meningiomas. |
| Result |
Experimental results show that the RI subunit of PKA is relatively evenly distributed in the entire cytoplasm in some tumors, while the RII subunit is relatively discrete and exhibits a high-concentration local distribution characteristic. Unlike normal brain tissue and other types of tumors, these aggregates can be visualized with fluorescent 8-substituted cAMP analogs under equilibrium binding conditions. By observing the PKA catalytic subunits in fixed sections, researchers found that the two catalytic subunits of PKA exhibited a distribution pattern that completely overlapped with that of RII. They also constructed a gene expression database to correlate the expression relationship between PKA subunits and meningioma-related genes, results showed that PKA catalytic subunits were significantly correlated with meningioma-related genes. Collectively, the experiments observed completely different cAMP binding properties, biochemical activities, and PKA profiles from the normal brain and other brain tumors, proposing the possibility of harnessing PKA intracellular pathways as a diagnostic tool and possible therapeutic intervention.
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Fig. 2 Observation of the distribution of proteins.2,3
References
- Image retrieved from Alphafold (Uniprot ID Q5UE93), used under CC BY 4.0, without any modification.
- Caretta, Antonio, et al. "Protein Kinase A distribution in meningioma." Cancers 11.11 (2019): 1686.
- Image retrieved from Figure 2 " Case 3 representative images. " Caretta, et al. 2019, used under CC BY 4.0. The original image was modified by extracting and using part a-f and the title was changed to " Observation of the distribution of proteins.".
