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)

Conventional myosin light chain kinase found in differentiated smooth and non-muscle cells is a dedicated Ca2+/calmodulin-dependent protein kinase which phosphorylates the regulatory light chain of myosin II. This phosphorylation increases the actin-activated myosin ATPase activity and is thought to play major roles in a number of biological processes, including smooth muscle contraction. The catalytic domain contains residues on its surface that bind a regulatory segment resulting in autoinhibition through an intrasteric mechanism. When Ca2+/calmodulin binds, there is a marked displacement of the regulatory segment from the catalytic cleft allowing phosphorylation of myosin regulatory light chain. Kinase activity depends upon Ca2+/calmodulin binding not only to the canonical calmodulin-binding sequence but also to additional interactions between Ca2+/calmodulin and the catalytic core. Previous biochemical evidence shows myosin light chain kinase binds tightly to actomyosin containing filaments. The kinase has low-affinity myosin and actin binding sites in Ig-like motifs at the N- and C-terminus, respectively. Recent results show the N-terminus of myosin light chain kinase is responsible for filament binding in vivo. However, the apparent binding affinity is greater for smooth muscle myofilaments, purified thin filaments, or actin-containing filaments in permeable cells than for purified smooth muscle F-actin or actomyosin filaments from skeletal muscle. These results suggest a protein on actin thin filaments that may facilitate kinase binding. Myosin light chain kinase does not dissociate from filaments in the presence of Ca2+/calmodulin raising the interesting question as to how the kinase phosphorylates myosin in thick filaments if it is bound to actin-containing thin filaments.
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PMID:Myosin light chain kinase: functional domains and structural motifs. 988 70

The sarcoplasmic reticulum (SR) plays a key role in excitation/contraction coupling of skeletal muscle. The SR is composed of two continuous yet heterogeneous membrane compartments, the free or longitudinal SR and cisternal SR. Cisternal SR is made up of free SR membrane, enriched in Ca(2+) pumps, and junctional SR (jSR) membrane, enriched in ryanodine-sensitive Ca(2+)-release channels, and contains calsequestrin within its lumen. Protein phosphorylation mediated by the Ca(2+)/calmodulin-dependent protein kinase II (CaM kinase II) has significant, distinct regulatory roles in both Ca(2+) uptake and Ca(2+) release. Kinase-anchoring proteins (KAPs) constitute a novel mechanism for achieving cell compartmentalization of effectors in phosphorylation pathways. Here, targeting of alpha KAP, a CaM kinase II-anchoring protein encoded within the alpha-CaM kinase II gene, was studied in transgenic skeletal muscle fibres of the adult rat soleus. The transgenes were epitope-tagged versions of alpha KAP and of a deletion mutant, allowing their specific immunodetection against the wild-type background. Our results show that alpha KAP is largely localized at the free SR and thus near the Ca(2+) pump, a protein that can be modulated by CaM kinase II phosphorylation. Only minor co-localization was observed with the jSR ryanodine-sensitive Ca(2+)-release channel, which is a potential CaM kinase II target. In non-muscle cells, recombinant alpha KAP is targeted to endoplasmic reticulum (ER). Both ER and SR targeting requires the N-terminal hydrophobic region of alpha KAP. An unexpected additional specific localization that does not require the N-terminus was found in the nucleus, providing a first clue of how CaM kinase II can fulfil its nuclear functions in skeletal muscle.
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PMID:Targeting of alpha-kinase-anchoring protein (alpha KAP) to sarcoplasmic reticulum and nuclei of skeletal muscle. 1247 Feb 97

Genome project terminated and post-genome project started, one of which aim is to understand the function and its regulation mechanism(s) of the molecules in living cells. Protein phosphorylation is one of the most common reactions responsive to extracellular stimulants. It is well understood about the involvement of Rho/Rho-kinase and Cdc42/p21-activated kinase (PAK) in the functions of muscle and non-muscle cells, but in neuronal cells little or poorly is understood. This is due to poor evidences about the target molecules of Rho-kinase and PAK and its functions in neuronal cells. We have revealed using a phosphorylation site-specific antibody that PAK targets synapsin Ia at Ser603 in vitro and in neuronal cells in culture, which is recognized as CaMKII site. This is reasonable, because the 600RQAS603 around Ser603 is also consensus motif for the phosphorylation of PAK and Rho-kinase besides CaMKII. Like this, we have tried to define the target molecules of Rho-kinase in neuronal cells. In this symposium, I would present that both Rho-kinase and PAK target MARCKS at Ser159 in vitro and in neuronal cells stimulated with LPA and bradykinin, respectively. Moreover, we would address the role of phosphorylation of MARCKS at Ser159 in neuronal functions.
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PMID:[Probing of the target molecules of Rho-kinase and its function in neuronal cells]. 1472 13