Calmodulin-Dependent Protein Kinase II Activation Promotes Kidney Mesangial Expansion in Streptozotocin-Induced Diabetic Mice

Cancer-induced bone pain is a severe and complex pain caused by metastases to bone in cancer patients. The aim of this study was to investigate the analgesic effect of scutellarin on cancer-induced bone pain in rat models by intrathecal injection of Walker 256 carcinoma cells. Mechanical allodynia was determined by paw withdrawal threshold in response to mechanical stimulus, and thermal hyperalgesia was indicated by paw withdrawal latency in response to noxious thermal stimulus. The paw withdrawal threshold and paw withdrawal latencies were significantly decreased after inoculation of tumor cells, whereas administration of scutellarin significantly attenuated tumor cell inoculation-induced mechanical and heat hyperalgesia. Tumor cell inoculation-induced tumor growth was also significantly abrogated by scutellarin. Ca2+/calmodulin-dependent protein kinase II is a multifunctional kinase with up-regulated activity in bone pain models. The activation of Ca2+/calmodulin-dependent protein kinase II triggers phosphorylation of cAMP-response element binding protein. Scutellarin significantly reduced the expression of phosphorylated-Ca2+/calmodulin-dependent protein kinase II and phosphorylated-cAMP-response element binding protein in cancer-induced bone pain rats. Collectively, our study demonstrated that scutellarin attenuated tumor cell inoculation-induced bone pain by down-regulating the expression of phosphorylated-Ca2+/calmodulin-dependent protein kinase II and phosphorylated-cAMP-response element binding protein. The suppressive effect of scutellarin on phosphorylated-Ca2+/calmodulin-dependent protein kinase II/phosphorylated-cAMP-response element binding protein activation may serve as a novel therapeutic strategy for CIBP management.

Potential Role of Calcium/Calmodulin-dependent Protein Kinase II to Angiogenesis Mediated Pathological Changes Seen in Osteoarthritis

Current Angiogenesis ◽

10.2174/2211552803666141110210138 ◽

2015 ◽

Vol 3 (3) ◽

pp. 123-131

Author(s):

Sadaf Ashraf

Keyword(s):

Protein Kinase ◽

Potential Role ◽

Pathological Changes ◽

Dependent Protein Kinase ◽

Calcium Calmodulin Dependent ◽

Protein Kinase Ii ◽

Dependent Protein

Calcium/Calmodulin-Dependent Protein Kinase II Involvement in Release of Gonadotropin-Releasing Hormone

Neuroendocrinology ◽

10.1159/000054309 ◽

1998 ◽

Vol 67 (2) ◽

pp. 145-152 ◽

Cited By ~ 8

Author(s):

Wendy W. Waters ◽

Pat L. Chen ◽

Newell H. McArthur ◽

Pete A. Moreno ◽

Paul G. Harms

Keyword(s):

Protein Kinase ◽

Gonadotropin Releasing Hormone ◽

Dependent Protein Kinase ◽

Releasing Hormone ◽

Calcium Calmodulin Dependent ◽

Protein Kinase Ii ◽

Dependent Protein

Identification and differential expression of two forms of regulatory subunits (RII) of cAMP-dependent protein kinase II in Friend erythroleukemic cells. Differentiation and 8-bromo-cAMP elicit a large and selective increase in the rate of biosynthesis of only one type of RII.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)88970-0 ◽

1985 ◽

Vol 260 (10) ◽

pp. 6296-6303 ◽

Cited By ~ 7

Author(s):

D A Schwartz ◽

C S Rubin

Keyword(s):

Protein Kinase ◽

Differential Expression ◽

Dependent Protein Kinase ◽

Regulatory Subunits ◽

Camp Dependent Protein Kinase ◽

Protein Kinase Ii ◽

Dependent Protein ◽

Friend Erythroleukemic Cells ◽

Selective Increase ◽

Erythroleukemic Cells

Phosphorylation and activation of a bovine tracheal anion channel by Ca2+/calmodulin-dependent protein kinase II.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)47067-6 ◽

1994 ◽

Vol 269 (43) ◽

pp. 26642-26650

Author(s):

C M Fuller ◽

I I Ismailov ◽

D A Keeton ◽

D J Benos

Keyword(s):

Protein Kinase ◽

Anion Channel ◽

Dependent Protein Kinase ◽

Protein Kinase Ii ◽

Dependent Protein

Reversible generation of a Ca2+-independent form of Ca2+(calmodulin)-dependent protein kinase II by an autophosphorylation mechanism.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)84416-2 ◽

1986 ◽

Vol 261 (19) ◽

pp. 8581-8584

Author(s):

C M Schworer ◽

R J Colbran ◽

T R Soderling

Keyword(s):

Protein Kinase ◽

Dependent Protein Kinase ◽

Independent Form ◽

Protein Kinase Ii ◽

Dependent Protein

Ca2+/Calmodulin-Dependent Protein Kinase II Is a Modulator of CARMA1-Mediated NF-κB Activation

Molecular and Cellular Biology ◽

10.1128/mcb.02469-05 ◽

2006 ◽

Vol 26 (14) ◽

pp. 5497-5508 ◽

Cited By ~ 72

Author(s):

Kazuhiro Ishiguro ◽

Todd Green ◽

Joseph Rapley ◽

Heather Wachtel ◽

Cosmas Giallourakis ◽

...

Keyword(s):

T Cell ◽

Protein Kinase ◽

T Cell Activation ◽

Cell Activation ◽

Cell Receptor ◽

Tcr Signaling ◽

Dependent Protein Kinase ◽

Immune Synapse ◽

Protein Kinase Ii ◽

Dependent Protein

ABSTRACT CARMA1 is a central regulator of NF-κB activation in lymphocytes. CARMA1 and Bcl10 functionally interact and control NF-κB signaling downstream of the T-cell receptor (TCR). Computational analysis of expression neighborhoods of CARMA1-Bcl10MALT 1 for enrichment in kinases identified calmodulin-dependent protein kinase II (CaMKII) as an important component of this pathway. Here we report that Ca2+/CaMKII is redistributed to the immune synapse following T-cell activation and that CaMKII is critical for NF-κB activation induced by TCR stimulation. Furthermore, CaMKII enhances CARMA1-induced NF-κB activation. Moreover, we have shown that CaMKII phosphorylates CARMA1 on Ser109 and that the phosphorylation facilitates the interaction between CARMA1 and Bcl10. These results provide a novel function for CaMKII in TCR signaling and CARMA1-induced NF-κB activation.