Developmental regulation of two isoforms of Ca2+/calmodulin-dependent protein kinase I β in rat brain

Løseth, Ole-Petter; Lecea, Luı́s de; Calbet, Marta; Danielson, Patria E.; Gautvik, Vigdis T.; Høvring, Per Ivar; Walaas, S. Ivar; Gautvik, Kaare M.

doi:10.1016/s0006-8993(00)02359-3

Cited by 13 publications

(7 citation statements)

References 21 publications

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“…In neurons, CaMKI is predominantly cytoplasmic (Picciotto et al, 1995); however, a splice variant of the ␤ isoform is nuclear (Rina et al, 2001), and the ␥ isoform can be associated with the Golgi and plasma membranes (TakemotoKimura et al, 2003). Developmentally, mRNA for CaMKI iso-forms in rat brain is present at embryonic day (E) 15, increases at E18, and peaks at postnatal day (P) 1-7 (Sawamura et al, 1996;Loseth et al, 2000). CaMKI is present in numerous brain regions, including hippocampal pyramidal and cerebellar granule neurons, cell types that are examined in this report.…”

Section: Introductionmentioning

confidence: 80%

Regulation of Axonal Extension and Growth Cone Motility by Calmodulin-Dependent Protein Kinase I

Wayman¹,

Kaech²,

Grant³

et al. 2004

J. Neurosci.

173

182

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Calcium and calmodulin (CaM) are important signaling molecules that regulate axonal or dendritic extension and branching. The Ca 2ϩ -dependent stimulation of neurite elongation has generally been assumed to be mediated by CaM-kinase II (CaMKII), although other members of the CaMK family are highly expressed in developing neurons. We have examined this assumption using a combination of dominant-negative CaMKs (dnCaMKs) and other specific CaMK inhibitors. Here we report that inhibition of cytosolic CaMKI, but not CaMKII or nuclear CaMKIV, dramatically decreases axonal outgrowth and branching in cultured neonatal hippocampal and postnatal cerebellar granule neurons. CaMKI is found throughout the cell cytosol, including the growth cone. Growth cones of neurons expressing dnCaMI or dnCaMKK, the upstream activator of CaMKI, exhibit collapsed morphology with a prominent reduction in lamellipodia. Live-cell imaging confirms that these morphological changes are associated with a dramatic decrease in growth cone motility. Treatment of neurons with 1,8-naphthoylene benzimidazole-3-carboxylic acid (STO-609), an inhibitor of CaMKK, causes a similar change in morphology and reduction in growth cone motility, and this inhibition can be rescued by transfection with an STO-609-insensitive mutant of CaMKK or by transfection with constitutively active CaMKI. These results identify CaMKI as a positive transducer of growth cone motility and axon outgrowth and provide a new physiological role for the CaMKK-CaMKI pathway.

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Section: Introductionmentioning

confidence: 80%

Regulation of Axonal Extension and Growth Cone Motility by Calmodulin-Dependent Protein Kinase I

Wayman¹,

Kaech²,

Grant³

et al. 2004

J. Neurosci.

173

182

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“…Members of the CaMK family also contain various isoforms by means of alternative splicing (39,40). The rat CaMK I␤ is differentially spliced into two isoforms (designated as ␤1 and ␤2) with distinct C termini (39,41). These isoforms are developmentally regulated, with the ␤1 isoform present in rat embryos from day 18 and the ␤2 isoform present from day 5 postnatally.…”

Section: Discussionmentioning

confidence: 99%

Human Ca2+/Calmodulin-dependent Protein Kinase Kinase β Gene Encodes Multiple Isoforms That Display Distinct Kinase Activity

Hsu¹,

Chen²,

Lee³

et al. 2001

Journal of Biological Chemistry

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Ca؉2 /calmodulin-dependent protein kinases (CaMKs) are activated upon binding of Ca ؉2 /calmodulin. To gain maximal activity, CaMK I and CaMK IV can be further phosphorylated by an upstream kinase, CaMK kinase (CaMKK). We previously isolated cDNA clones encoding human CaMKK ␤ isoforms that are heterogeneous in their 3-sequences (Hsu, L.-S., Tsou, A.-P., Chi, C.-W., Lee, C.-H., and Chen, J.-Y. (1998) J. Biomed. Sci. 5, 141-149). In the present study, we examined the genomic organization and transcription of the human CaMKK ␤ gene. The human CaMKK ␤ locus spans more than 40 kilobase pairs and maps to chromosome 12q24.2. It is organized into 18 exons and 17 introns that are flanked by typical splice donor and acceptor sequences. Two major species of transcripts, namely the ␤1 (5.6 kilobase pairs) and ␤2 (2.9 kilobase pairs), are generated through differential usage of polyadenylation sites located in the last and penultimate exons. Additional forms of CaMKK ␤ transcripts were also identified that resulted from alternative splicing of the internal exons 14 and/or 16. These isoforms display differential expression patterns in human tissues and tumor-derived cell lines. They also exhibit a distinct ability to undergo autophosphorylation and to phosphorylate the downstream kinases CaMK I and CaMK IV. The differential expression of CaMKK ␤ isoforms with distinct activity further suggests the complexity of the regulation of the CaMKK/CaMK cascade and an important role for CaMKK in the action of Ca ؉2 -mediated cellular responses.

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“…It is the most homologous to calmodulin kinase I within the catalytic domain and predominantly expressed in the central nervous system. [14], [15] On the basis of studies, PNCK is found to play a role in cytoplasmic and nuclear signal transduction. [16], [17] However, the detailed molecular and genetic understanding of how PNCK contributes to the malignant ccRCC remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Increased Expression of Pregnancy Up-Regulated Non-Ubiquitous Calmodulin Kinase Is Associated with Poor Prognosis in Clear Cell Renal Cell Carcinoma

Wang

et al. 2013

PLoS ONE

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PurposeThe aims of this study were to evaluate the clinical significance and potential prognostic value of pregnancy up-regulated non-ubiquitous calmodulin kinase (PNCK) in clear cell renal cell carcinoma (ccRCC) patients.Materials and MethodsThe expression of PNCK mRNA was determined in 24 paired samples of ccRCCs and adjacent normal tissues using real-time RT-PCR. The expression of PNCK was determined in 248 samples of ccRCCs and 92 paired samples of adjacent normal tissues by immunohistochemical analysis. Statistical analysis was performed to define the relationship between PNCK expression and the clinical features of ccRCC.ResultsThe mRNA level of PNCK was significantly higher in tumorous tissues than in the adjacent non-tumorous tissues (p<0.001). An immunohistochemical analysis of 92 paired tissue specimens showed that PNCK expression was higher in tumorous tissues than in the adjacent non-tumorous tissues (p<0.001). Moreover, there was a significant correlation between the PNCK expression and various clinicopathological parameters such as Fuhrman grade (p = 0.011), tumor size (p<0.001), T stage (p<0.001) and N stage (p = 0.015). Patients with higher PNCK expression had shorter overall survival time than those with lower PNCK expression (p<0.001). Multivariate analysis indicated that PNCK expression was an independent predictor for poor survival of ccRCC patients.ConclusionsTo our knowledge, this is the first study that determines the relationship between PNCK and prognosis in ccRCC. We found that increased PNCK expression is associated with poor prognosis in ccRCC. PNCK may represent a novel prognostic marker for ccRCC.

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Developmental regulation of two isoforms of Ca2+/calmodulin-dependent protein kinase I β in rat brain

Cited by 13 publications

References 21 publications

Regulation of Axonal Extension and Growth Cone Motility by Calmodulin-Dependent Protein Kinase I

Regulation of Axonal Extension and Growth Cone Motility by Calmodulin-Dependent Protein Kinase I

Human Ca2+/Calmodulin-dependent Protein Kinase Kinase β Gene Encodes Multiple Isoforms That Display Distinct Kinase Activity

Increased Expression of Pregnancy Up-Regulated Non-Ubiquitous Calmodulin Kinase Is Associated with Poor Prognosis in Clear Cell Renal Cell Carcinoma

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