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Myocardin belongs to the SAF-A/B, Acinus, PIAS (SAP) domain family of transcription factors and is specifically expressed in cardiac and smooth muscle. Myocardin functions as a transcriptional coactivator of SRF and is sufficient and necessary for smooth muscle gene expression. We have previously found that myocardin induces the acetylation of nucleosomal histones surrounding SRF-binding sites in the control regions of cardiac and smooth muscle genes through recruiting chromatin- modifying enzyme p300, yet no studies have determined whether myocardin itself is similarly modified. In this study, we show that myocardin is a direct target for p300-mediated acetylation. p300 acetylates lysine residues at the N terminus of the myocardin protein. Interestingly, a direct interaction between p300 and myocardin, which is mediated by the C terminus of myocardin, is required for the acetylation event. Acetylation of myocardin by p300 enhances the association of myocardin and SRF as well as the formation of the myocardin-SRF-CArG box ternary complex. Conversely, acetylation of myocardin decreases the binding of histone deacetylase 5 (HDAC5) to myocardin. Acetylation of myocardin is required for myocardin to activate smooth muscle genes. Our study demonstrates that acetylation plays a key role in modulating myocardin function in controlling cardiac and smooth muscle gene expression. [ABSTRACT FROM AUTHOR]

Why some species become successful invaders is an important issue in invasive biology. However, limited genomic resources make it very difficult for identifying candidate genes involved in invasiveness. Mikania micrantha H.B.K. (Asteraceae), one of the world's most invasive weeds, has adapted rapidly in response to novel environments since its introduction to southern China. In its genome, we expect to find outlier loci under selection for local adaptation, critical to dissecting the molecular mechanisms of invasiveness. An explorative amplified fragment length polymorphism (AFLP) genome scan was used to detect candidate loci under selection in 28 M. micrantha populations across its entire introduced range in southern China. We also estimated population genetic parameters, bottleneck signatures, and linkage disequilibrium. In binary characters, such as presence or absence of AFLP bands, if all four character combinations are present, it is referred to as a character incompatibility. Since character incompatibility is deemed to be rare in populations with extensive asexual reproduction, a character incompatibility analysis was also performed in order to infer the predominant mating system in the introduced M. micrantha populations. Out of 483 AFLP loci examined using stringent significance criteria, 14 highly credible outlier loci were identified by Dfdist and Bayescan. Moreover, remarkable genetic variation, multiple introductions, substantial bottlenecks and character compatibility were found to occur in M. micrantha. Thus local adaptation at the genome level indeed exists in M. micrantha, and may represent a major evolutionary mechanism of successful invasion. Interactions between genetic diversity, multiple introductions, and reproductive modes contribute to increase the capacity of adaptive evolution. [ABSTRACT FROM AUTHOR]

Microcystin-LR (MCLR) and linear alkylbenzene sulfonate (LAS) are present widely in aquatic and terrestrial ecosystems, but their combined ecotoxicological risk is unknown. This study investigated the toxic effects of MCLR, LAS and their mixture on lettuce ( Lactuca sativa L .) and evaluated MCLR accumulation level in lettuce with or without LAS. The changes in seed germination and shoot/root growth, responses of the antioxidative defense system, and the accumulation of MCLR in lettuce were tested to evaluate the single and combined toxic effect of MCLR and LAS in well-controlled conditions. The results showed that seedling growth (except for root elongation and leaf weight) was more sensitive to toxicant exposure than seed germination. For seedling leaves, lipid peroxidation was not observed when the antioxidative defense system (including superoxide dismutase, catalase and glutathione) was activated to relieve the adverse effects of oxidative stress via different pathways. Our results also confirmed that the interaction between MCLR and LAS was synergistic. Both toxicants in combination not only significantly inhibited seedling growth, but also increased the activities of superoxide dismutase and catalase, as well as the contents of glutathione. Furthermore, LAS dramatically enhanced the accumulation of MCLR in the plant, thus leading to a reduction in quality and yield and posing greater potential risk to humans via consumption of these edible plants. [ABSTRACT FROM AUTHOR]

Transient receptor potential A1 (TRPA1) forms nonselective cation channels implicated in acute inflammatory pain and nociception. The mechanism of ligand activation of TRPA1 may involve either covalent modification of cysteine residues or conventional reversible ligand–receptor interactions. For certain electrophilic prostaglandins, covalent modification has been considered as the main mechanism involved in their stimulatory effect on TRPA1. Because some nonsteroidal anti-inflammatory drugs (NSAIDs) are structural analogs of prostaglandins, we examined several nonelectrophilic NSAIDs on TRPA1 activation using electrophysiological techniques and intracellular Ca2+ measurements and found that a selected group of NSAIDs can act as TRPA1 agonists. Extracellularly applied flufenamic, niflumic, and mefenamic acid, as well as flurbiprofen, ketoprofen, diclofenac, and indomethacin, rapidly activated rat TRPA1 expressed in Xenopus oocytes and human TRPA1 endogenously expressed in WI-38 fibroblasts. Similarly, the NSAID ligands activated human TRPA1 inducibly expressed in HEK293 cells, but the responses were absent in uninduced and parental HEK293 cells. The response to fenamate agonists was blocked by TRPA1 antagonists, AP-18, HC-030031, and ruthenium red. At subsaturating concentrations, the fenamate NSAIDs also potentiate the activation of TRPA1 by allyl isothiocyanate, cinnamaldehyde, and cold, demonstrating positive synergistic interactions with other well-characterized TRPA1 activators. Importantly, among several thermosensitive TRP channels, the stimulatory effect is specific to TRPA1 because flufenamic acid inhibited TRPV1, TRPV3, and TRPM8. We conclude that fenamate NSAIDs are a novel class of potent and reversible direct agonists of TRPA1. This selective group of TRPA1-stimulating NSAIDs should provide a structural basis for developing novel ligands that noncovalently interact with TRPA1 channels. [ABSTRACT FROM AUTHOR]

Amyloid-beta peptide (Aβ) is known to induce the redox imbalance, mitochondrial dysfunction and caspase activation, resulting in neuronal cell death. Treatment with antioxidants provided a new therapeutic strategy for Alzheimer’s disease (AD) patients. Here we investigate the effects of purple sweet potato anthocyanins (PSPA), the known strong free radical scavengers, on Aβ toxicity in PC12 cells. The results showed that pretreatment of PC12 cells with PSPA reduced Aβ-induced toxicity, intracellular reactive oxygen species (ROS) generation and lipid peroxidation dose-dependently. In parallel, cell apoptosis triggered by Aβ characterized with the DNA fragmentation and caspase-3 activity were also inhibited by PSPA. The concentration of intracellular Ca2+ and membrane potential loss associated with cell apoptosis were attenuated by PSPA. These results suggested that PSPA could protect the PC-12 cell from Aβ-induced injury through the inhibition of oxidative damage, intracellular calcium influx, mitochondria dysfunction and ultimately inhibition of cell apoptosis. The present study indicates that PSPA may be a promising approach for the treatment of AD and other oxidative-stress-related neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

In [Z. Cai, C. Tong, P. S. Vassilevski, and C. Wang, Numer. Methods Partial Differential Equations, to appear], the authors developed and analyzed a mixed finite element method for the stationary Stokes equations based on the pseudostress-velocity formulation. The pseudostress and the velocity are approximated by a stable pair of finite elements: Raviart-Thomas elements of index k ≥ 0 and discontinuous piecewise polynomials of degree k ≥ 0, respectively. This paper extends the method to the stationary, incompressible Navier-Stokes equations. Under appropriate assumptions, we show that the pseudostress-velocity formulation of the Navier-Stokes equation and its discrete counterpart have branches of nonsingular solutions, and error estimates of the mixed finite element approximations are established as well. [ABSTRACT FROM AUTHOR]

Background and objective Drugs which block tumor angiogenesis will be likely effective towards inhibiting tumor growth for angiogenesis being a prerequisite for tumor growth and metastasis. Therefore, antiangiogenesis has become a promising strategy for the treatment of cancer. Investigation on both antiangiogenic effect and mechanism(s) of oyster polypeptide (OPP) were performed via experiments of chicken embryos model in vivo and human umbilical vein endothelial cells (HUVECs) in vitro. Methods The methods employed in experiment were chorioallantoic membrane (CAM) angiogenesis in chicken embryos in vivo, MTT cell survival assay, flat plate scarification, transwell plates assay, matrigel-induced tube formation assay and transmission electron microscope et al. and the OPP's effects on angiogenesis was observed. Results Study showed that treatment with OPP resulted in significant inhibition of chorioallantoic membrane (CAM) angiogenesis in chicken embryos. MTT cell survival assay showed that treatment with OPP resulted in strong inhibition of HUVECs growth, with an IC50 of 400 μg/mL. Flat plate scarification suggested that OPP (200 μg/mL, 400 μg/mL and 800 μg/mL) distinctly inhibited HUVECs' migration (18.75%, 37.93%, 74.07% respectively, treatment for 12 h). Treatment with OPP of different concentrations (200 μg/mL, 400 μg/mL and 800 μg/mL) significantly reduced the density of the migration cells by 15.5%, 37.2% and 67.24% (P<0.05) respectively. Matrigel-induced tube formation assay showed that OPP resulted in striking inhibition of tube formation of 52.43%, 84.47% and 96.12% (P<0.01) at 200 μg/mL, 400 μg/mL and 800 μg/mL (treatment for 10 h) respectively. In addition, the apoptotic analysis by transmission electron microscope showed that OPP (400 μg/mL, treatment for 48 h) distinctly induced HUVECs' apoptosis. Conclusion This study strikingly showed that OPP could inhibit angiogenesis through its effects on vascular endothelial cells directly and the inhibition of their proliferation, migration, angiogenic ability, and induction of their apoptosis might be the antiangiogenic mechanism of OPP. [ABSTRACT FROM AUTHOR]

A correction to this paper has been published: https://doi.org/10.1007/s11368-021-02986-z [ABSTRACT FROM AUTHOR]

Recent studies suggest that lysozyme, rich in hen egg, has an antitumor function. In the present study, we investigated the antitumor and antiangiogenesis effects of a newly isolated marine lysozyme both in vitro and in vivo. First, we showed that this marine-derived lysozyme specifically inhibits the proliferation of endothelial cells (ECV304) in a dose-dependent manner with no cytotoxicity (IC50 = 3.64 μM). Second, we showed that this marine lysozyme directly suppresses neovascularization in chicken embryos using chorioallantoic membrane assay. Third, we demonstrated that this marine lysozyme markedly inhibits tumor growth in mice bearing either sarcoma 180 or hepatoma 22. Unexpectedly, hen egg lysozyme has no effects on the proliferation of endothelial cells in vitro or neovascularization in chicken embryos or tumor growth in nude mice at the same dosage range. Taken together, our studies clearly show that the newly identified marine lysozyme is a potent antitumor molecule, which may inhibit tumor growth and inhibit angiogenesis. We believe that this marine lysozyme may have a therapeutic value in antitumor drug development. [ABSTRACT FROM AUTHOR]

Solar ultraviolet (UV) radiation is a major environmental factor that causes DNA damage, inflammation, erythema, sunburn, immunosuppression, photoaging, gene mutations, and skin cancer. p38 mitogen activated protein kinase (MAPK) are strongly activated by UV radiation, and play important roles in regulating cellular responses to UV. In this review, we examine the role played by p38 MAPK in mediating UV-induced cell cycle, apoptosis, inflammation, and skin tanning response . We review the role played by p38 MAPK in transcriptional regulation of key downstream genes that have been implicated in the regulation of cellular responses to UV radiation. Understanding this will undoubtedly help in the prevention and control of UV-induced damage and the development of novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Transient receptor potential vanilloid (TRPV) channels are polymodal detectors of multiple environmental factors, including temperature, pH, and pressure. Inflammatory mediators enhance TRPV function through multiple signaling pathways. The lipoxygenase and epoxygenase products of arachidonic acid (AA) metabolism have been shown to directly activate TRPV1 and TRPV4, respectively. TRPV3 is a thermosensitive channel with an intermediate temperature threshold of 31–39°C. We have previously shown that TRPV3 is activated by 2-aminoethoxydiphenyl borate (2APB). Here we show that AA and other unsaturated fatty acids directly potentiate 2APB-induced responses of TRPV3 expressed in HEK293 cells, Xenopus oocytes, and mouse keratinocytes. The AA-induced potentiation is observed in intracellular Ca2+ measurement, whole-cell and two-electrode voltage clamp studies, as well as single channel recordings of excised inside-out and outside-out patches. The fatty acid-induced potentiation is not blocked by inhibitors of protein kinase C and thus differs from that induced by the kinase. The potentiation does not require AA metabolism but is rather mimicked by non-metabolizable analogs of AA. These results suggest a novel mechanism regulating the TRPV3 response to inflammation, which differs from TRPV1 and TRPV4, and involves a direct action of free fatty acids on the channel. J. Cell. Physiol. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Background: Sphingolipids are key molecules regulating many essential functions in eukaryotic cells and ceramide plays a central role in sphingolipid metabolism. A sphingolipid metabolism occurs in the intraerythrocytic stages of Plasmodium falciparum and is associated with essential biological processes. It constitutes an attractive and potential target for the development of new antimalarial drugs. Methods: The anti-Plasmodium activity of a series of ceramide analogs containing different linkages (amide, methylene or thiourea linkages) between the fatty acid part of ceramide and the sphingoid core was investigated in culture and compared to the sphingolipid analog PPMP (d,1-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol). This analog is known to inhibit the parasite sphingomyelin synthase activity and block parasite development by preventing the formation of the tubovesicular network that extends from the parasitophorous vacuole to the red cell membrane and delivers essential extracellular nutrients to the parasite. Results: Analogs containing methylene linkage showed a considerably higher anti-Plasmodium activity (IC50 in the low nanomolar range) than PPMP and their counterparts with a natural amide linkage (IC50 in the micromolar range). The methylene analogs blocked irreversibly P. falciparum development leading to parasite eradication in contrast to PPMP whose effect is cytostatic. A high sensitivity of action towards the parasite was observed when compared to their effect on the human MRC-5 cell growth. The toxicity towards parasites did not correlate with the inhibition by methylene analogs of the parasite sphingomyelin synthase activity and the tubovesicular network formation, indicating that this enzyme is not their primary target. Conclusions: It has been shown that ceramide analogs were potent inhibitors of P. falciparum growth in culture. Interestingly, the nature of the linkage between the fatty acid part and the sphingoid core considerably influences the antiplasmodial activity and the selectivity of analogs when compared to their cytotoxicity on mammalian cells. By comparison with their inhibitory effect on cancer cell growth, the ceramide analogs might inhibit P. falciparum growth through modulation of the endogenous ceramide level. [ABSTRACT FROM AUTHOR]

The indoles plant growth hormones have exhibited potentially antitumor activities. However, the targets of these indoles have not been clearly elucidated. By introduction of hydroxamic acid group to the structure of indolebutyric acid, the derived molecule (IBHA) exhibited potent HDAC2 (IC50 value of 0.32 ± 0.02 μM) and HDAC3 (IC50 value of 0.14 ± 0.01 μM) inhibitory activities compared with SAHA (IC50 value of 1.25 ± 0.06 μM and 0.97 ± 0.04 μM against HDAC2 and HDAC3). In the antiproliferative assays, the tested hematologic cell lines (U937 and K562) are more sensitive to IBHA than the solid tumor cell lines (MDA-MB-231 and PC-3). In the docking studies, the derived molecule (IBHA) could bind to the active site of human HDAC2 and HDAC3 by strong H-bond interactions and hydrophobic interactions. Pharmacophore mapping results revealed that properties of IBHA matches the receptor (HDAC3) based pharmacophore model. [ABSTRACT FROM AUTHOR]

Transient receptor potential channels are involved in sensing chemical and physical changes inside and outside of cells. TRPV3 is highly expressed in skin keratinocytes, where it forms a nonselective cation channel activated by hot temperatures in the innocuous and noxious range. The channel has also been implicated in flavor sensation in oral and nasal cavities as well as being a molecular target of some allergens and skin sensitizers. TRPV3 is unique in that its activity is sensitized upon repetitive stimulations. Here we investigated the role of calcium ions in the sensitization of TRPV3 to repetitive stimulations. We show that the sensitization is accompanied by a decrease of Ca2+-dependent channel inhibition mediated by calmodulin acting at an N-terminal site (amino acids 108-130) and by an acidic residue (Asp641) at the pore loop of TRPV3. These sites also contribute to the voltage dependence of TRPV3. During sensitization, the channel displayed a gradual shift of the voltage dependence to more negative potentials as well as uncoupling from voltage sensing. The initial response to ligand stimulation was increased and sensitization to repetitive stimulations was decreased by increasing the intracellular Ca2+-buffering strength, inhibiting calmodulin, or disrupting the calmodulin-binding site. Mutation of Asp641 to Asn abolished the high affinity extracellular Ca2+-mediated inhibition and greatly facilitated the activation of TRPV3. We conclude that Ca2+ inhibits TRPV3 from both the extracellular and intracellular sides. The inhibition is sequentially reduced, appearing as sensitization to repetitive stimulations. [ABSTRACT FROM AUTHOR]

The transient receptor potential (TRP) superfamily contains a large number of proteins encoding cation permeable channels that are further divided into TRPC (canonical), TRPM (melastatin), and TRPV (vanilloid) subfamilies. Among the six TRPV members, TRPV1, TRPV2, TRPV3, and TRPV4 form heat-activated cation channels, which serve diverse functions ranging from nociception to osmolality regulation. Although chemical activators for TRPV1 and TRPV4 are well documented, those for TRPV2 and TRPV3 are lacking. Here we show that in the absence of other stimuli, 2-aminoethoxydiphenyl borate (2APB) activates TRPV1, TRPV2, and TRPV3, but not TRPV4, TRPV5, and TRPV6 expressed in HEK293 cells. In contrast, 2APB inhibits the activity of TRPC6 and TRPM8 evoked by 1-oleolyl-2-acetyl-sn-glycerol and menthol, respectively. In addition, low levels of 2APB strongly potentiate the effect of capsaicin, protons, and heat on TRPV1 as well as that of heat on TRPV3 expressed in Xenopus oocytes. In dorsal root ganglia neurons, supra-additive stimulations were evoked by 2APB and capsaicin or 2APB and acid. Our data suggest the existence of a common activation mechanism for TRPV1, TRPV2, and TRPV3 that may serve as a therapeutic target for pain management and treatment for diseases caused by hypersensitivity and temperature misregulation. [ABSTRACT FROM AUTHOR]

Aerobic anoxygenic phototrophic (AAP) bacteria are known functionally as photoheterotrophic microbes. Though numerously reported from ocean habitats, their distribution in freshwater lakes is far less documented. In the present study we investigated the dynamics of AAP bacteria in freshwater plateau lakes. Results revealed a high abundance of AAP bacteria in eutrophic lakes. Moreover, AAP bacteria were positively correlated with TN, TP, and Chl a, but the variations of AAP bacterial proportion to potential total bacteria (AAPB%). Alphaproteobacteria-related sequences dominated lakes Luguhu, Erhai, and Chenghai at ratios of 93.9, 85.4, and 70.6%, respectively, and in total comprised eight clearly defined subgroups. Sequences affiliated with Beta- and Grammaproteobacteria were found to be rare taxa. Additionally, Alkalibacterium-like sequences belonging to Firmutes were assigned. Overall, sequences from Alpha-, Beta-, Gammaproteobacteria, and Firmutes separately comprised of 81.6, 8.8, 0.8, and 4.0%. Our present work revealed extreme dynamics of AAP bacteria in both water columns and non-euphotic sediments of plateau aquatic ecosystems, which consolidated their wide distribution and enhanced adaptation. [ABSTRACT FROM AUTHOR]

Occurrences of harmful cyanobacterial blooms are a worldwide environmental problem in most eutrophic lake ecosystems. But what should be noticed is that cyanobacteria can be used as a useful resource due to the wide range of metabolites they produce. Nutrient partitioning using purple nonsulfur bacteria (PNSB) has the potential to biologically concentrate nutrients. The present study evaluated the kinetics of nutrients released from decomposed field blue green algae (BGA) biomasses. The potential of nutrient acquisition from decomposed BGA biomasses for culturing Rhodopseudomonas palustris (R. palustris) was investigated via fed-batch experiments. Results indicated that R. palustris stimulated in algae substrates with algae biomasses ranging from 3.33 to 10 g/L. Removal efficiencies of N and P in the stationary phase of growth were at least 40% and 95%, respectively, of all the nitrogen (N) and phosphorus (P) released. Additionally, the cellular contents like total lipid and poly-β-hydroxybutyrate (PHB), as well as the fatty acids produced by R. palustris, were consistent. Hence, practice based on the bacterial production for the nutrient recovery from BGA biomasses provides a new insight in field algae disposal. It will lower the chances of secondary pollution due to algae decay and produce giant cells of R. palustris and surely will prosper the industries applying R. palustris. [ABSTRACT FROM AUTHOR]

TRPV1 and TRPV3 are two heat-sensitive ion channels activated at distinct temperature ranges perceived by human as hot and warm, respectively. Compounds eliciting human sensations of heat or warmth can also potently activate these channels. In rodents, TRPV3 is expressed predominantly in skin keratinocytes, whereas in humans TRPV1 and TRPV3 are co-expressed in sensory neurons of dorsal root ganglia and trigeminal ganglion and are known to form heteromeric channels with distinct single channel conductances as well as sensitivities to TRPV1 activator capsaicin and inhibitor capsazepine. However, how heteromericTRPV1/TRPV3channels respond to heat and other stimuli remains unknown. In this study, we examined the behavior of heteromeric TRPV1/TRPV3 channels activated by heat, capsaicin, and voltage. Our results demonstrate that the heteromeric channels exhibit distinct temperature sensitivity, activation threshold, and heat-induced sensitization. Changes in gating properties apparently originate from interactions between TRPV1 and TRPV3 subunits. Our results suggest that heteromeric TRPV1/TRPV3 channels are unique heat sensors that may contribute to the fine-tuning of sensitivity to sensory inputs. [ABSTRACT FROM AUTHOR]

Transient receptor potential channel melastatin subfamily (TRPM) 4 and its close homologue, TRPM5, are the only two members of the large transient receptor potential superfamily of cation channels that are impermeable to Ca2+. In this study, we located the TRPM4 selectivity filter and investigated possible structural elements that render it Ca2+-impermeable-Based on homology with known cation channel pores, we identified an acidic stretch of six amino acids in the loop between transmembrane helices TM5 and TM6 (981EDMDVA986) as a potential selectivity filter. Substitution of this six-amino acid stretch with the selectivity filter of TRPV6 (TIIDGP) resulted in a functional channel that combined the gating hallmarks of TRPM4 (activation by Ca2+, voltage dependence) with TRPV6-like sensitivity to block by extracellular Ca2+ and Mg2+ as well as Ca2+ permeation. Neutralization of Glu981 resulted in a channel with normal permeability properties but a strongly reduced sensitivity to block by intracellular spermine. Neutralization of Asp982 yielded a functional channel that exhibited extremely fast desensitization (τ < 5 s), possibly indicating destabilization of the pore. Neutralization of Asp984 resulted in a non-functional channel with a dominant negative phenotype when coexpressed with wild type TRPM4. Combined neutralization of all three acidic residues resulted in a functional channel whose voltage dependence was shifted toward very positive potentials. Substitution of Gin977 by a glutamate, the corresponding residue in divalent cation-permeable TRPM channels, altered the monovalent cation permeability sequence and resulted in a pore with moderate Ca2+ permeability. Our findings delineate the selectivity filter of TRPM channels and provide the first insight into the molecular basis of monovalent cation selectivity. [ABSTRACT FROM AUTHOR]

TRPM4, a Ca2+-activated cation channel of the transient receptor potential superfamily, undergoes a fast desensitization to Ca2+. The mechanisms underlying the alterations in Ca2+ sensitivity are unknown. Here we show that cytoplasmic ATP reversed Ca2+ sensitivity after desensitization, whereas mutations to putative ATP binding sites resulted in faster and more complete desensitization. Phorbol ester-induced activation of protein kinase C (PKC) increased the Ca2+ sensitivity of wild-type TRPM4 but not of two mutants mutated at putative PKC phosphorylation sites. Overexpression of a calmodulin mutant unable to bind Ca2+ dramatically reduced TRPM4 activation. We identified five Ca2+-calmodulin binding sites in TRPM4 and showed that deletion of any of the three C-terminal sites strongly impaired current activation by reducing Ca2+ sensitivity and shifting the voltage dependence of activation to very positive potentials. Thus, the Ca2+ sensitivity of TRPM4 is regulated by ATP, PKC-dependent phosphorylation, and calmodulin binding at the C terminus. [ABSTRACT FROM AUTHOR]