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Protein phosphatase 1 regulatory subunit 1B (PPP1R1B), also known as dopamine- and cAMP-regulated neuronal phosphoprotein (DARPP32), is a protein that plays a crucial role in multiple brain functions. It is encoded by the PPP1R1B gene and is primarily found in midbrain dopaminergic neurons. Abnormal signaling through dopaminergic pathways has been implicated in various neurological and psychiatric disorders, making PPP1R1B an essential protein of interest in the field of neuroscience.
In a study investigating neurotransmitter actions in the brain, researchers discovered a 32-kDa protein. It is abundantly expressed in neostriatal spiny neurons and regulated by dopamine and cAMP, leading to its designation as DARPP32. In addition to its expression in the brain, DARPP32 is also found in the adrenal medulla, kidney, and parathyroid cells. The protein's primary function is to inhibit protein phosphatase-1 (PP1) after being phosphorylated at the Thr-34 residue by protein kinase A (PKA). Therefore, DARPP32 is also known as PPP1R1B. DARPP32 has been shown to play a crucial role in mediating the biochemical, electrophysiological, and behavioral effects of dopamine on dopaminoceptive neurons. Additionally, it has been implicated in the actions of other neurotransmitter systems, such as serotonin and glutamate, as well as in the response to various drugs of abuse.
DARPP32 is widely known as a protein that plays a crucial role in mediating neurotransmitter interactions in the brain. However, recent research has expanded its relevance to cancer. The amplification of the genomic locus of DARPP32 has been observed in several types of cancers, including breast, prostate, colon, and stomach adenocarcinomas. Moreover, DARPP32 and its truncated isoform, t-DARPP (missing the first 36 amino acids at the N-terminus), are frequently overexpressed at both mRNA and protein levels in these cancers. Studies have demonstrated that DARPP32 promotes pro-survival, pro-invasion, and pro-angiogenic functions in cancer cells. Additionally, its overexpression has been associated with chemotherapeutic drug resistance and enhanced cell proliferation in gastric and breast cancers, affecting the pro-oncogenic signal transduction pathways. These findings suggest that DARPP32 may serve as a valuable biomarker and potential therapeutic target in cancer treatment, highlighting its clinical significance in understanding and combating this disease.
Figure 1. DARPP-32 regulates major hallmarks of tumorigenesis.
(Source: Belkhiri, A. et al., 2016)
Dysfunction in the dopamine system and imbalance in DARPP32 phosphorylation and dephosphorylation are associated with abnormal psychiatric behavior. This imbalance adjustment is believed to be beneficial for the treatment of central nervous system diseases, including schizophrenia. Promoting DARPP32 phosphorylation can be achieved by stimulating or blocking neurotransmitter receptors or inhibiting phosphodiesterases (PDEs) that degrade cAMP, the second messenger involved in DARPP32 activity. PDE4 inhibitors such as rolipram show promise but have side effects. Novel PDE4 inhibitors with fewer side effects are being explored. Studies on DARPP32 phosphorylation and protein expression in schizophrenia provide insights for therapeutic strategies. Increasing DARPP32 expression, possibly through BDNF activation, may be beneficial. DARPP32 is considered a major signaling protein in the CNS and a promising therapeutic target for CNS disorders, including schizophrenia.
Reference
| Target | Cat. No. | Product Name | Expression System | Tag/Conjugate | Application | |
| Dopamine | DWT74 | Dopamine HCl Standard solution | N/A | N/A | Inquiry | |
| DAG3302 | Dopamine [BSA] | N/A | BSA | IHC, ICC | Inquiry | |
| Serotonin | DAGB349 | Serotonin [HRP] | N/A | HRP | IA | Inquiry |
| DAG3405 | 5-Hydroxytryptamine [BSA] | N/A | BSA | ICC, IHC | Inquiry | |
| CAMP | DAG-P0248 | Human CAMP peptide | N/A | Unconjugated | ELISA | Inquiry |
| CDBP0697 | Human CAMP blocking peptide | N/A | Unconjugated | BL | Inquiry | |
| CDBP5261 | CAMP blocking peptide | N/A | Unconjugated | IB | Inquiry |
| Target | Cat. No. | Product Name | Size | Species | Application | Detection Sample | |
| PPP1R1B | DEIA-XYA531 | DARPP-32 ELISA Kit | 96T | Qualitative | Cultured cells | Inquiry | |
| DEIA-XYA532 | DARPP-32 (Phospho-Thr34) ELISA Kit | 2 x 96T | Qualitative | Cultured cells | Inquiry | ||
| DEIA-XYA533 | DARPP-32 (Phospho-Thr75) ELISA Kit | 2 x 96T | Qualitative | Cultured cells | Inquiry | ||
| Dopamine | DEIA2011 | Tricat (Adrenalin, Noradrenalin, Dopamine) ELISA Kit | 96T | Human | Quantitative | Plasma, urine | Inquiry |
| Serotonin | DEIA6182 | Serotonin high sensitive ELISA Kit | 96T | Quantitative | Tissues homogenates, dialysates | Inquiry | |
| DEIA2014 | Serotonin ELISA Kit | 96T | Reacts with all species | Quantitative | Various biological sample types | Inquiry | |
| DEIA2236 | Serotonin ELISA Kit | 96T | Human | Quantitative | Serum, plasma, platelets, urine | Inquiry | |
| DEIA2144 | Serotonin FAST ELISA Kit | 96T | Quantitative | Serum, urine, platelets | Inquiry | ||
| DEIA-NS2307-36 | Rat 5-hydroxytryptamine ELISA Kit | 96T | Rat | Quantitative | Serum, plasma, tissue homogenates and other biological fluids. | Inquiry | |
| DEIA-NS2307-35 | Mouse 5-hydroxytryptamine ELISA Kit | 96T | Mouse | Quantitative | Serum, plasma, cell culture supernatant and other biological samples. | Inquiry | |
| DEIA-NS2307-34 | Human 5-hydroxytryptamine ELISA Kit | 96T | Human | Quantitative | Serum, plasma, tissue homogenates and other biological fluids. | Inquiry | |
| CAMP | DEIA-NS2307-96 | Human CAMP(Cathelicidin Antimicrobial Peptide) ELISA Kit | 96T | Human | Quantitative | Serum, plasma, cell culture supernatant and other biological samples. | Inquiry |
| DEIA2964 | Mouse/Rat cAMP ELISA Kit | 96T | Mouse, Rat | Quantitative | Cell culture supernates, cell lysates, tissue homogenates, plasma, and urine | Inquiry | |
| DEIA2692 | cAMP ELISA Kit | 96T | Quantitative | Cell culture supernatants, cell lysates, Serum, plasma, saliva, urine | Inquiry | ||
| DEIA2174 | Human LL-37 ELISA Kit | 96T | Human | Quantitative | Serum | Inquiry | |
| DEIA-LL089 | Horse CATHL1 (Cathelicidin-1) ELISA Kit | 96T | Horse | Quantitative | Serum, plasma, tissue homogenates and other biological fluids | Inquiry |
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