New isoforms of Ca2+/calmodulin-dependent protein kinase II in smooth muscle

Abstract

Four novel isoforms of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) were found in rat aorta smooth muscle. Two of them were related to gamma-isoform of brain CaM kinase II (gamma-a). Differences in the primary structure of these isoforms were located in the variable region. One of them (gamma-b) contained 23 unique amino acid residues, whereas the other (gamma-c) did not contain this sequence. Both isoforms lacked the two segments (Val-316 to Gln-337 and Lys-353 to Leu-362) present in gamma-a. The DNA sequence of these gamma-isoforms except the variable region was exactly the same, suggesting that they are produced by alternative splicing. Another two isoforms were related to the delta-isoform of brain CaM kinase II (delta-a). delta-b contained a unique 11-residue sequence in the variable region whereas delta-c did not. As found for gamma-isoforms, the sequence analysis suggested that the three delta-isoforms are also produced by alternative splicing. Analysis of RNA by reverse transcription PCR confirmed the existence of specific messages for gamma-b, delta-a and delta-b. The variety of isoforms of CaM kinase II suggest that each isoform may play a specialized role in cell regulation.

Altered mRNA expression for brain-derived neurotrophic factor and type II calcium/Calmodulin-dependent protein kinase in the hippocampus of patients with intractable temporal lobe epilepsy

“…CamKII is one of the most abundant kinases in the central nervous system (CNS), comprising as much as 2% of total forebrain protein (Kelly, 1991;Schulman and Hanson, 1993). Initially isolated as a multimeric holoenzyme of ␣ and ␤ subunits, recent studies have identified two additional subunits, ␦ and ␥, as well as a series of alternatively spliced isoforms (Tobimatsu et al, 1988;Tobimatsu and Fujisawa, 1989;Benson et al, 1991;Mayer et al, 1993;Zhou and Ikebe, 1994). The ␣CamKII and ␤CamKII subunits are the most abundant throughout the brain and are localized within the same excitatory neuronal populations as BDNF mRNA, including all subfields of the hippocampus and the dentate gyrus as well as the amygdala and most layers and regions of cortex (Erondu and Kennedy, 1985;Ouimet et al, 1984;Benson et al, 1992b).…”

The Multifunctional Ca2+/Calmodulin-dependent Kinase II δ (CaMKIIδ) Controls Neointima Formation after Carotid Ligation and Vascular Smooth Muscle Cell Proliferation through Cell Cycle Regulation by p21

“…1, A, right panel and B). CaMKII isoforms ␥ and ␦ are reported to be expressed in arteries (22,23), therefore we performed qRT-PCR to identify which isoforms are up-regulated after carotid ligation. 14 days after surgery, CaMKII␦ mRNA was increased by 42.6%ϩ3.6% (p Ͻ 0.05) whereas CaMKII␥ mRNA was unchanged in response to ligation (Fig.…”

Ryanodine receptor 2 contributes to hemorrhagic shock-induced bi-phasic vascular reactivity in rats

“…In VSMCs, freeCaM binding with Ca 2+ could accelerate the formation of the CaM-CaM related kinase II (CaMK II) complex, a ubiquitous multifunctional serine/threonine kinase expressed in VSMCs as multimers of γ-and/or δ-sun units [29] , and increase MLCK activity and MLC20 phosphorylation, which contribute to vascular contraction [30] . However, Ca 2+ release located next to cytomembranes, also known as Ca 2+ spark, triggers the formation of STOCs [31] and activates the large conductance calcium activated potassium channel (BK Ca ), which at least partially contributes to the vascular hyporeactivity observed after hemorrhagic shock [32] .…”