Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.17 (CaMKII)
 4,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Ca2+/calmodulin dependent protein kinase II (CaM kinase II) is thought to play an important part in glucose-stimulated insulin secretion. To determine which of the known subtypes (alpha, beta, gamma, delta) occur in insulin-secreting cells, we amplified all types of CaM kinase II by RT-PCR and found the beta3-, gamma-, delta2- and delta6-subtypes in RINm5F insulinoma cells. None of the other 8 delta-subtypes was present. Antibodies generated against the bacterially expressed association domain of the delta2-subtype recognized the recombinant gamma and delta-subtypes. In INS-1 and RINm5F cells, as well as freshly isolated rat islets, only a 55-kDa protein corresponding in size to the delta2-subtype expressed in NIH3T3 fibroblasts was detected. The delta2-subtype therefore appears to represent the predominant subtype of CaM kinase II present in insulin secreting cells. The enzyme was primarily associated with cytoskeletal structures, and very little was present in the soluble compartment or detergent soluble fraction in INS-1- or RINm5F-cells. An analysis of its subcellular distribution was performed by sucrose and Nycodenz density gradient fractionation of INS-1 cells and detection of CaM kinase II delta by immune blots. The enzyme codistributed with insulin used as a marker for secretory granules but not with the lighter synaptic-like microvesicles detected with an antibody against synaptophysin, plasma membranes (syntaxin 1), lysosomes (arylsulfatase), or mitochondria (cytochrome c oxidase). CaM kinase II delta2 thus is identified as the subtype associated with insulin secretory granules and is likely to be involved in insulin secretion.
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PMID:Insulinoma cells contain an isoform of Ca2+/calmodulin-dependent protein kinase II delta associated with insulin secretion vesicles. 916 51

Notch signaling is associated with prostate osteoblastic bone metastases and calcium/calmodulin-dependent kinase II (CaMKII) is associated with osteoblastogenesis of human mesenchymal stem cells. Here we show that prostate cancer cell lines C4-2B and PC3, both derived from bone metastases and express Notch-1, have all four isoforms of CaMKII (alpha, beta, gamma, delta). In contrast, prostate cancer cell lines LNcaP and DU145, which are not derived from bone metastases and lack the Notch-1 receptor, both lack the alpha isoform of CaMKII. In addition, DU145 cells also lack the beta-isoform. In C4-2B cells, inhibition of CaMKII by KN93 or gamma-secretase by L-685,458 inhibited the formation of the cleaved form of Notch-1 thus inhibiting Notch signaling. KN93 inhibited down stream Notch-1 signaling including Hes-1 gene expression, Hes-1 promoter activity, and c-Myc expression. In addition, both KN93 and L-685,458 inhibited proliferation and Matrigel invasion by C4-2B cells. The activity of gamma-secretase was unaffected by KN93 but markedly inhibited by L-685,458. Inhibition of the expression of alpha, beta, or gamma-isoform by siRNA did not affect Hes-1 gene expression, however when expression of one isoform was inhibited by siRNA, there were compensatory changes in the expression of the other isoforms. Over-expression of CaMKII-alpha increased Hes-1 expression, consistent with Notch-1 signaling being at least partially dependent upon CaMKII. This unique crosstalk between CaMKII and Notch-1 pathways provides new insight into Notch signaling and potentially provides new targets for pharmacotherapeutics.
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PMID:Calcium/calmodulin-dependent kinase II regulates notch-1 signaling in prostate cancer cells. 1902 Nov 44