Calcium/Calmodulin-Stimulated Protein Kinase II (CaMKII): Different Functional Outcomes from Activation, Depending on the Cellular Microenvironment

Abstract

Calcium/calmodulin-stimulated protein kinase II (CaMKII) is a family of broad substrate specificity serine (Ser)/threonine (Thr) protein kinases widely expressed in many tissues that is capable of mediating diverse functional responses depending on its cellular and molecular microenvironment. This review briefly summarises current knowledge on the structure and regulation of CaMKII and focuses on how the molecular environment, and interaction with binding partner proteins, can produce different populations of CaMKII in different cells, or in different subcellular locations within the same cell, and how these different populations of CaMKII can produce diverse functional responses to activation following an increase in intracellular calcium concentration. This review also explores the possibility that identifying and characterising the molecular interactions responsible for the molecular targeting of CaMKII in different cells in vivo, and identifying the sites on CaMKII and/or the binding proteins through which these interactions occur, could lead to the development of highly selective inhibitors of specific CaMKII-mediated functional responses in specific cells that would not affect CaMKII-mediated responses in other cells. This may result in the development of new pharmacological agents with therapeutic potential for many clinical conditions.

The Effect of SERCA Activation on Functional Characteristics and Signaling of Rat Soleus Muscle upon 7 Days of Unloading

“…CaMKII regulates the phosphorylation of several proteins, including AMPK [ 53 , 55 , 56 ] and some transcription factors [ 57 ]. Increased calcium concentrations induce autophosphorylation of CaMK IIβ at Thr 287 [ 58 ]. Treatment of rats with CDN1163 in the current study prevented an increase in the level of CaMK IIβ phosphorylation.…”

Different recovery patterns of the surviving bivalve Mytilus galloprovincialis based on transcriptome profiling exposed to spherical or fibrous polyethylene microplastics

“…The initial stages of MP exposure in the organisms demonstrated an increase in the levels of CAMK genes. CAMK controls neurotransmitter synthesis and regulates cellular processes, the cell cycle, and differentiation [ 51 , 52 ]. The Ca 2+ binding proteins, members of the neuronal calcium sensor protein family, have anti-apoptotic signaling response functions involving the MAP-K signaling pathway [ 53 , 54 ].…”

Osteoblast-lineage calcium/calmodulin-dependent kinase 2 delta and gamma regulates bone mass and quality

“…Likewise, our previously reported regulation of sclerostin protein abundance downstream of CaMKII involved posttranslational control. Notably, CaMKII plays an important role in protein trafficking and secretion in neuronal cells and pancreatic beta-cells ( 52 ) and may serve a similar, largely unexplored role in bone.…”