Controlling the cell cycle: The role of calcium/calmodulin-stimulated protein kinases I and II

Abstract

Many studies have implicated Ca²+ and calmodulin (CaM) as regulators of the cell cycle. Ca²+/CaM-stimulated proteins, including the family of multifunctional Ca²+/CaM-stimulated protein kinases (CaMK), have also been identified as mediators of cell cycle progression. CaMKII is the best-characterized member of this family, and is regulated by multi-site phosphorylation and targeting. Using pharmacological inhibitors that were believed to be specific for CaMKII, CaMKII has been implicated in every phase of the cell cycle. However, these 'specific' inhibitors also produce effects on other CaMKs. These additional effects are usually ignored, and the effects of the inhibitors are normally attributed to CaMKII without further investigation. Using new specific molecular techniques, it has become clear that CaMKI is an important regulator of G₁, whereas CaMKII is essential for regulating G₂/M and the metaphase-anaphase transition. If the mechanisms controlling these events can be fully elucidated, new targets for controlling proliferative diseases may be identified.

Calcium/calmodulin-dependent protein kinase II (CaMKII) phosphorylates Raf-1 at serine 338 and mediates Ras-stimulated Raf-1 activation

“…18,19 This kinase is one of the most abundant protein in the brain, where it is associated to neuronal functions, such as memory. Most of the studies on CaMKII focused on its role in neuronal cells.…”

Germinal center kinases in immune regulation

“…82 Meanwhile, Striatin can also bind to calmodulin (a calcium-binding protein that regulates the functions of many kinases), phosphotases, ion channels and other proteins in a calcium-dependent manner. [83][84][85] We have postulated that PDCD10 may cross-talk with FAK. …”

Ca2+ coding and decoding strategies for the specification of neural and renal precursor cells during development

“…For example, EF-hand proteins such as calmodulin (CaM) and CaM kinase (CaMK) are known to play a role in early neurogenesis (review in [91]), whereas calbindin-D28K and S100 are involved during neuronal differentiation and neurite outgrowth later on in development [92,93]. With regards to kidney development, Ca 2+ signalling has largely been studied through the characterization of Ca 2+ -binding proteins such as the senescence marker protein-30 (SMP30), calretinin, calbindin 1 and 2, parvalbumin, S100 and annexin IV [94,95].…”