CAMK-like (CAMKL) family

CAMK, also known as CaMK, is an abbreviation for enzymes in the Ca²⁺/calmodulin-dependent protein kinase class. It is a serine/threonine-specific protein kinase that is regulated by the calcium/calmodulin complex. This germline protein exhibits a memory effect when activated. CAMK is activated by increasing the concentration of intracellular calcium (Ca²⁺) and calmodulin. Upon activation, these enzymes transfer phosphate from ATP to serine or threonine residues defined in other proteins, so they are serine / threonine-specific protein kinases. Activated CAMK is involved in the phosphorylation of transcription factors and is therefore involved in the regulation of expression of response genes. CAMK can also regulate the life cycle of cells (i.e., programmed cell death), rearrangement of the cytoskeletal network, and mechanisms involved in learning and memory of organisms.

Types

There are two types of calmodulin kinases:

Specific calmodulin kinase: for example, myosin light chain kinase, which can phosphorylate myosin and cause muscle contraction. Versatile Calmodulin Kinase: These proteins are also collectively known as CalM kinase II, and they play an important role in many biological reactions. Such as the secretion of neurotransmitters, the regulation of transcription factors and glycogen metabolism. About 1% to 2% of the protein in the brain is calmodulin kinase II.

Structure

Calmodulin kinase includes an N-terminal catalytic region, a regulatory region, and a combined region.

CAMK1

Calcium / calmodulin-dependent protein kinase type 1 is an enzyme encoded by the CAMK1 gene in humans. calmodulin-dependent protein kinase I is expressed in many tissues and is part of the calmodulin-dependent protein kinase cascade. Calcium / calmodulin directly activates calcium/calmodulin-dependent protein kinase I through binding to enzymes, and indirectly promotes the phosphorylation and synergistic activation of calcium / calmodulin-dependent protein kinase I kinase.

Figure 1. Protein structure of CAMK1.

CAMKII

The sensitivity of the CaMKII enzyme to calcium and calmodulin is controlled by variable and self-associated domains. This sensitivity level of CaMKII will also regulate different activation states of the enzyme. Initially, the enzyme is activated; however, since there is not enough calcium or calmodulin to bind to an adjacent subunit, autophosphorylation does not occur. With the accumulation of a large amount of calcium and calmodulin, autophosphorylation occurs, resulting in continuous activation of CaMKII enzyme for a short period of time. However, the threonine 286 residue was eventually dephosphorylated, causing CaMKII inactivation.

Figure 2. The structure of the kinase domain of CaMKII.

CAMKIII

Eukaryotic elongation factor 2 kinase (eEF-2 kinase or eEF-2K), also known as calmodulin-dependent protein kinase III (CAMKIII) and calcium/calmodulin-dependent eukaryotic elongation factor 2 kinase, which is a human enzyme eEF-2 kinase, a highly conserved protein kinase in the calmodulin-mediated signaling pathway, linking multiple upstream signals to the regulation of protein synthesis. It phosphorylates eukaryotic elongation factor 2 (EEF2), thereby inhibiting EEF2 function. The activity of this kinase is increased in many cancers and may be a valid target for anti-cancer treatment. It is also suggested that eEF-2K may play a role the rapid anti-depressant effects of ketamine through its regulation of neuronal protein synthesis.

CAMKIV

Calcium/calmodulin-dependent protein kinase type IV is an enzyme encoded by the CAMK4 gene in the human body. The product of this gene belongs to the serine / threonine protein kinase family and belongs to the Ca²⁺/ calmodulin-dependent protein kinase (CAMK) subtype. Branch. This enzyme is a multifunctional serine/threonine protein kinase with limited tissue distribution and is involved in the transcriptional regulation of lymphocytes, neurons and male germ cells.

Reference

1. Swulius MT; et al. Ca(2+)/calmodulin-dependent protein kinases. Cellular and Molecular Life Sciences. 2008, 65 (17): 2637–57.