ArticleRNA biology
Differential effects of PKA-controlled CaMKK2 variants on neuronal differentiation.
Article in RNA biology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- The Rbfox1/LASR complex controls alternative pre-mRNA splicing by recognition of multipart RNA regulatory modules.Genes & development · 2025Article
- Improvements in Exercise for Alzheimer's Disease: Highlighting FGF21-Induced Cerebrovascular Protection.Neurochemical research · 2025Review
- Brain-derived neurotrophic factor protects neurons by stimulating mitochondrial function through protein kinase A.Journal of neurochemistry · 2023Article
- Regulation and role of CAMKK2 in prostate cancer.Nature reviews. Urology · 2022Review
- Cell type-specific abnormalities of central nervous system in myotonic dystrophy type 1.Brain communications · 2022Article
- A complete map of the Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) signaling pathway.Journal of cell communication and signaling · 2021Article
- Prox1 inhibits neurite outgrowth during central nervous system development.Cellular and molecular life sciences : CMLS · 2021Article
- Motor Stereotypic Behavior Was Associated With Immune Response in Macaques: Insight From Transcriptome and Gut Microbiota Analysis.Frontiers in microbiology · 2021Article
- Article
- Muscarinic Toxin 7 Signals Via CaMolecular neurobiology · 2020Article
- CAMKK2-CAMK4 signaling regulates transferrin trafficking, turnover, and iron homeostasis.Cell communication and signaling : CCS · 2020Article
- Systematic Analyses of the Differentially Expressed Alternative Splicing Events in Gastric Cancer and Its Clinical Significance.Frontiers in genetics · 2020Article
- Loss of CaFrontiers in molecular biosciences · 2018Article
- SMN regulation in SMA and in response to stress: new paradigms and therapeutic possibilities.Human genetics · 2017Review
- Autophosphorylation of CaMKK2 generates autonomous activity that is disrupted by a T85S mutation linked to anxiety and bipolar disorder.Scientific reports · 2015Article
- Convergent lines of evidence support CAMKK2 as a schizophrenia susceptibility gene.Molecular psychiatry · 2014Article
- Quantitative-proteomic comparison of alpha and Beta cells to uncover novel targets for lineage reprogramming.PloS one · 2014Article
- Emerging mechanisms and consequences of calcium regulation of alternative splicing in neurons and endocrine cells.Cellular and molecular life sciences : CMLS · 2013Review
- Inhibition of Ca²⁺/calmodulin-dependent protein kinase kinase 2 stimulates osteoblast formation and inhibits osteoclast differentiation.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2013Article
- Calcium/calmodulin-dependent protein kinase kinase 2: roles in signaling and pathophysiology.The Journal of biological chemistry · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Regulation between protein kinases is critical for the establishment of signaling pathways/networks to 'orchestrate' cellular processes. Besides posttranslational phosphorylation, alternative pre-mRNA splicing is another way to control kinase properties, but splicing regulation between two kinases and the effect of resulting variants on cells has barely been explored. Here we examined the effect of the protein kinase A (PKA) pathway on the alternative splicing and variant properties of the Ca²⁺/calmodulin-dependent protein kinase kinase 2 (CaMKK2) gene in B35 neuroblastoma cells. Inclusion of the exon 16 of CaMKK2 was significantly reduced by H89, a PKA selective inhibitor. Consistently, overexpressed PKA strongly promoted the exon inclusion in a CaMKK2 sequence-dependent way in splicing reporter assays. In vitro, purified CaMKKβ1 variant proteins were found to be kinase-active. In cells, they were differentially phosphorylated by PKA. In RNA interference assays, CaMKKβ1 was found to be essential for forskolin-induced neurite growth. Interestingly, overexpression of the variant without exon 16 (-E16) promoted neurite elongation while the other one (+E16) promoted neurite branching; in contrast, reduction of the latter one enhanced neurite elongation. Moreover, the variants are differentially expressed and the exon 16-containing transcripts highly enriched in the brain, particularly the cerebellum and hippocampus. Thus, PKA regulates the alternative splicing of CaMKK2 to produce variants that differentially modulate neuronal differentiation. Taken together with the many distinct variants of kinases, alternative splicing regulation likely adds another layer of modulation between protein kinases in cellular signaling networks.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.