CaMK
Calcium is a major second messenger in all cells, and is integral in many important signalling pathways. Changes in intracellular Ca2+ regulate many biological processes, including neurotransmitter release, gene expression, and the cell cycle. Though free Ca2+ can activate a number of proteins directly (for example myosin, phospholipase A2, and protein kinase C), it regulates the activity of many enzymes indirectly via a number of low molecular weight Ca2+ binding proteins, the most abundant of which is calmodulin (CaM). There are three main families of restricted Ca2+/CaM stimulated protein kinases: phosphorylase kinase (PhK), elongation factor 2 kinase (eEF2K) and myosin light chain kinase (MLCK). The most basic method of controlling kinase function is via the regulation of Ca2+ dynamics, specifically the frequency, amplitude and duration of oscillations in the intracellular concentration of Ca2+.
The multifunctional Ca2+/CaMstimulated protein kinase II (CaMKII) can translate the frequency of Ca2+ spikes into corresponding amounts of kinase activity.The multifunctional calcium/calmodulin stimulated protein kinases can be classified into two broad families based on the homology of their domain structures.The four kinases which form one family – calcium/calmodulin stimulated protein kinase kinase (CaMKK) and calcium/calmodulin stimulated protein kinase I, IV and II (CaMKI, CaMKIV and CaMKII). Calcium/calmodulin stimulated protein kinase kinase (CaMKK) is a multifunctional protein kinase encoded by two genes (CAMKK1 and CAMKK2) that produce CaMKKα and CaMKKβ, respectively. CaMKK, CaMKI and CaMKIV have been shown to form a signalling pathway termed the Ca2+/CaM-dependent kinase cascade, which has been implicated in several cellular processes, including axonal and dendritic outgrowth and elongation, adiposity regulation, glucose homeostasis, hematopoietic stem cell maintenance, cell proliferation, apoptosis, and normal immune cell function.
References
1.Kaestner L,et al. Adv Exp Med Biol. 2020;1131:625-648.
The multifunctional Ca2+/CaMstimulated protein kinase II (CaMKII) can translate the frequency of Ca2+ spikes into corresponding amounts of kinase activity.The multifunctional calcium/calmodulin stimulated protein kinases can be classified into two broad families based on the homology of their domain structures.The four kinases which form one family – calcium/calmodulin stimulated protein kinase kinase (CaMKK) and calcium/calmodulin stimulated protein kinase I, IV and II (CaMKI, CaMKIV and CaMKII). Calcium/calmodulin stimulated protein kinase kinase (CaMKK) is a multifunctional protein kinase encoded by two genes (CAMKK1 and CAMKK2) that produce CaMKKα and CaMKKβ, respectively. CaMKK, CaMKI and CaMKIV have been shown to form a signalling pathway termed the Ca2+/CaM-dependent kinase cascade, which has been implicated in several cellular processes, including axonal and dendritic outgrowth and elongation, adiposity regulation, glucose homeostasis, hematopoietic stem cell maintenance, cell proliferation, apoptosis, and normal immune cell function.
References
1.Kaestner L,et al. Adv Exp Med Biol. 2020;1131:625-648.
Endocrinology/Hormones
CaMK
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Elziverine
catalog no : M36165
cas no: 95520-81-3
Elziverine is an orally available small molecule calmodulin antagonist. -
Cloxacepride
catalog no : M36150
cas no: 65569-29-1
cloxacepride is a CaM antagonist that is used to treat asthma disease. -
KN-93 Phosphate B
catalog no : M34125
cas no: 1913269-12-1
KN-93 (Phosphate) can competitively block the binding of calmodulin to the corresponding kinase. It is a calcium/calmodulin-dependent kinase II (CaMKII) inhibitor with a Ki of 370 nM. -
Autocamtide-2-related inhibitory peptide, myristoylated
catalog no : M30768
cas no: 201422-04-0
CaM kinase II inhibitor; enhanced cell permeable derivative of Autocamtide-2-related inhibitory peptide. Pretreatment blocks reinstatement of morphine-seeking behavior in vivo. -
MLCK inhibitor peptide 18
catalog no : M30641
cas no: 224579-74-2
Selective competitive inhibitor of myosin light chain kinase (IC50 = 50 nM). Displays 4000-fold selectivity over CaM kinase II and does not inhibit PKA. Cell permeable.