A calmodulin-like protein as an extracellular mitogen for the keratinocyte

Goberdhan, N.J.; Dawson, Rebecca; Frkedlander, E.; Neil, S. Mac

doi:10.1111/j.1365-2133.1993.tb03331.x

Cited by 35 publications

(21 citation statements)

References 27 publications

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“…It may stimulate the proliferation of cultured hepatocytes, keratinocytes, melanoma cells, K562 leukemia cells, HUVECs, and fibroblasts (39,(41)(42)(43)(44)(45). However, effects of calmodulin on inflammatory responses have not previously been described, and the effects of calmodulin on other monocyte and neutrophil functions, and on other cell types, are not known.…”

Section: Discussionmentioning

confidence: 99%

Endothelial Cells and Extracellular Calmodulin Inhibit Monocyte Tumor Necrosis Factor Release and Augment Neutrophil Elastase Release

Houston

Carson

Esmon

1997

Journal of Biological Chemistry

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Cultured human umbilical vein endothelial cells inhibited tumor necrosis factor-␣ release from whole blood or isolated mononuclear cells exposed to endotoxin. In contrast, the endothelial cells augmented neutrophil elastase release in the same blood. A protein with these functional properties was isolated from endothelial cell-conditioned media and, surprisingly, was identified as calmodulin. Authentic calmodulin mimicked the effect of endothelium.125 I-Calmodulin bound to a high affinity site on monocytic cell lines (K d ϳ30 nM, in agreement with its functional activity). Cross-linking of 125 I-calmodulin to monocytic cells identified a candidate calmodulin receptor. We conclude that calmodulin possesses an extracellular signaling role in addition to its intracellular regulatory functions. Calmodulin released at sites of tissue injury or possibly by specific mechanisms in the endothelium can bind to receptors, modulating the activities of inflammatory cells.

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Section: Discussionmentioning

confidence: 99%

Endothelial Cells and Extracellular Calmodulin Inhibit Monocyte Tumor Necrosis Factor Release and Augment Neutrophil Elastase Release

Houston

Carson

Esmon

1997

Journal of Biological Chemistry

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“…[6][7][8] Defined keratinocyte-serum free medium (SFM) (Invitrogen, UK; calcium concentration 0.09 mM) supplemented with 100 IU/mL penicillin and 100 mg/mL streptomycin was used for both NHK and Ha-Cat cell cultures. The concentration of calcium in the medium was increased from 0.09 mM to 2 mM by the addition of calcium chloride.…”

Section: Cell Culturementioning

confidence: 99%

Modeling the Effect of Exogenous Calcium on Keratinocyte and HaCat Cell Proliferation and Differentiation Using an Agent-Based Computational Paradigm

et al. 2006

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In this study we sought to develop a computational modeling paradigm in order to describe the influence of calcium on normal and transformed keratinocyte proliferation and differentiation. Keratinocytes and HaCat cells were grown in monolayer cultures with low and physiologic calcium concentrations, and levels of proliferation and involucrin expression were assessed. Both types of cells grew as monolayers under a low-calcium environment, and stratified in media with physiologic levels of calcium. However, keratinocytes were more proliferative in low rather than physiologic levels of calcium, whereas the opposite was true for HaCat cells. Normal keratinocytes differentiated as calcium levels increased. HaCat cells showed little differentiation at any calcium concentration. However, while the computer simulation could be modified to describe the effect of calcium on the growth of normal keratinocytes, our findings did not support the hypothesis that simply "turning off" the ability of HaCat cells to differentiate would account for the growth characteristics of these transformed cells. This demonstrates the application of computational modeling to hypothesis testing in biological systems.

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“…Recently, it has been found that CaM exists extracellularly to exert many functions in both animals and plants. In animals, extracellular CaM (ExtCaM) is present in body fluids, saliva, urine, and milk (Houston et al, 1997), stimulating the proliferation of cultured hepatocytes, melanoma cells, and fibroblasts (Goberdhan et al, 1993). In addition, ExtCaM inhibits tumor necrosis factor-a release and augments neutrophil elastase release, preventing further cytotoxicity (Houston et al, 1997).…”

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confidence: 99%

Extracellular Calmodulin-Induced Stomatal Closure Is Mediated by Heterotrimeric G Protein and H2O2

et al. 2004

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Extracellular calmodulin (ExtCaM) exerts multiple functions in animals and plants, but the mode of ExtCaM action is not well understood. In this paper, we provide evidence that ExtCaM stimulates a cascade of intracellular signaling events to regulate stomatal movement. Analysis of the changes of cytosolic free Ca 21 ([Ca 21 (McAinsh et al., 1995;Grabov and Blatt, 1998). Accumulating evidence indicates that many stimuli enhance [Ca 21 ] cyt increase in guard cells (Rudd and Franklin-Tong, 2001); however, the upstream components of calcium signaling are not well understood.Heterotrimeric G proteins composed of a-, b-, and g-subunits are a key intracellular signaling molecule in eukaryotic cells. The activation by G-protein-coupled receptor results in conformation change of the Ga protein due to GTP binding and the separation of Ga from the Gbg dimer. GTP hydrolysis by GTPase activity of Ga results in the reassociation of Ga with Gbg (Jones and Assmann, 2004). In plants, G protein has been found to be involved in ion-channel regulation (Aharon et al., 1998;Wang et al., 2001), control of seed germination (Ullah et al., 2002), pollen tube elongation (Ma et al., 1999), and responses to ABA . Genome sequencing revealed the existence of only one prototypical Ga (GPA1) in Arabidopsis (Arabidopsis thaliana; Ma et al., 1990). It was reported that Ga-subunit-null mutants, gpa1-1 and gpa1-2, were insensitive to ABA inhibition of whole-cell inward K 1 currents and pH-independent ABA-activation of anion channels , suggesting Ga is a key component in ABA signaling. It is unknown whether Ga-subunit participates in calcium signaling in ABA regulation of guard cell responses.Recently, reactive oxygen species (ROS) has been shown to be an important second messenger in signaling to developmental processes, such as polar growth of Fucus rhizoid cells (Coelho et al., 2002) and cell elongation in root growth (Demidchik et al., 2003), responses to environmental stresses (BaxterBurrell et al., 2002), and guard cell movement (Pei et al., 2000). Evidence indicates that homeostasis of ROS depends on the activity of several enzymes involved in ROS generation as well as the activity of ROS scavenging enzymes (for review, see Mittler, 2002). Recently, guard cell-specific NADPH oxidases AtrbohD (Arabidopsis respiratory burst oxidase homologs D) and AtrbohF have been identified, and the double mutants of atrbohD/F are impaired in ABA-induced ROS generation, [Ca 21 ] cyt increases, and stomatal closing (Kwak et al., 2003), suggesting that AtrbohD and AtrbohF NADPH oxidases and ROS play an important 1 This work was supported by the Major State Basic Research Program of China (grant no. G1999011704) and by the National Science Foundation of China (grant no. 30370129).2 These authors contributed equally to the paper. * Corresponding author; e-mail xcwang@cau.edu.cn; fax 86-10-62733450.Article, publication date, and citation information can be found at www.plantphysiol.org/cgi

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A calmodulin-like protein as an extracellular mitogen for the keratinocyte

Cited by 35 publications

References 27 publications

Endothelial Cells and Extracellular Calmodulin Inhibit Monocyte Tumor Necrosis Factor Release and Augment Neutrophil Elastase Release

Endothelial Cells and Extracellular Calmodulin Inhibit Monocyte Tumor Necrosis Factor Release and Augment Neutrophil Elastase Release

Modeling the Effect of Exogenous Calcium on Keratinocyte and HaCat Cell Proliferation and Differentiation Using an Agent-Based Computational Paradigm

Extracellular Calmodulin-Induced Stomatal Closure Is Mediated by Heterotrimeric G Protein and H2O2

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