Preface

Chapter 7 **Calcium Signaling Initiated by Agonists in Mesenchymal Stromal Cells from the Human Adipose Tissue 139** Polina D. Kotova, Olga A. Rogachevskaja, Marina F. Bystrova, Ekaterina N. Kochkina, Denis S. Ivashin and Stanislav S. Kolesnikov

Cretoiu, Nicolae Suciu and Beatrice Mihaela Radu

Adrian Dumitru, Daniela Oana Toader, Sanda Maria Cretoiu, Dragos

Chapter 8 **Alterations in Calcium Signaling Pathways in**

**Breast Cancer 165**

**VI** Contents

Since the development of microelectronic clamping methodology and fluorescent indicators for direct measurement of dynamic intracellular calcium transients, our understanding of biological signal transduction has progressed dramatically since the 1980s. Calcium is a uni‐ versal signal in biology that modulates gene expression, transmitter and hormone release, muscular movement, and even "programmed" cell death. This book contains 8 carefully re‐ viewed chapters from a diverse set of expert biologists throughout the world who have con‐ ducted research in the general area of calcium signaling in organisms ranging from bacteria to humans. In accord with priorities of resolving human disease, the reader will also benefit from learning calcium's role in cellular signaling pathology relating to acute or chronic con‐ ditions such as vomiting, sepsis, obesity, hypertension, and cancer.

We wish to thank our expert contributors for their time and effort to share their research and knowledge. Also, we express our gratitude to the Intech staff including Lucija Tomicic-Dromgool (Commissioning Editor) for the editorial invitation and to Danijela Sakic (Pub‐ lishing Process Manager) for fielding all correspondence in order to make this book possible.

> **John N. Buchholz, PhD and Erik J. Behringer, PhD** Loma Linda University School of Medicine USA

**Section 1**

**Calcium Signaling in Multiple Cellular Models**

**Calcium Signaling in Multiple Cellular Models**

**Chapter 1**

**Provisional chapter**

**Regulation of Calcium Signaling by STIM1 and ORAI1**

STIM1 and ORAI1 proteins are regulators of intracellular Ca2+ mobilization. This Ca2+ mobilization is essential to shape Ca2+ signaling in eukaryotic cells. STIM1 is a transmembrane protein located at the endoplasmic reticulum, where it acts as an intraluminal Ca2+ sensor. The transient drop of intraluminal Ca2+ concentration triggers STIM1 activation, which relocates to plasma membrane-endoplasmic reticulum junctions to bind and activate ORAI1, a plasma membrane Ca2+ channel. Thus, the Ca2+ influx pathway mediated by STIM1/ORAI1 is termed store-operated Ca2+ entry (SOCE). STIM and ORAI proteins are also involved in non-SOCE Ca2+ influx pathways, as we discuss here. In this chapter, we review the current knowledge regarding the role of SOCE, STIM1, and ORAI1 in cell signaling, with special focus on the modulation of the activity of kinases, phosphatases, and transcription factors that are strongly influenced by the extracellular Ca2+ influx

Cell signaling is the network of reactions and interaction of molecules that allow cells to react to a wide range of stimuli. In this response, many pathways are involved, so cells are able to adapt to changing conditions. One of the mechanisms to respond to external stimuli is mediated by receptors, that is, proteins located at the plasma membrane that communicate the extracellular and the intracellular medium. A significant strategy that cells acquired early in their evolution was the modification of the composition of the intracellular milieu, so the ionic

**Regulation of Calcium Signaling by STIM1 and ORAI1**

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

DOI: 10.5772/intechopen.78587

Francisco Javier Martin-Romero,

Eulalia Pozo-Guisado

**Abstract**

**1. Introduction**

http://dx.doi.org/10.5772/intechopen.78587

mediated by these regulators.

**Keywords:** calcium, signaling, SOCE, STIM, ORAI

Carlos Pascual-Caro, Aida Lopez-Guerrero,

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

Noelia Espinosa-Bermejo and Eulalia Pozo-Guisado

Francisco Javier Martin-Romero, Carlos Pascual-Caro, Aida Lopez-Guerrero, Noelia Espinosa-Bermejo and

#### **Regulation of Calcium Signaling by STIM1 and ORAI1 Regulation of Calcium Signaling by STIM1 and ORAI1**

DOI: 10.5772/intechopen.78587

Francisco Javier Martin-Romero, Carlos Pascual-Caro, Aida Lopez-Guerrero, Noelia Espinosa-Bermejo and Eulalia Pozo-Guisado Francisco Javier Martin-Romero, Carlos Pascual-Caro, Aida Lopez-Guerrero, Noelia Espinosa-Bermejo and Eulalia Pozo-Guisado

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.78587

#### **Abstract**

STIM1 and ORAI1 proteins are regulators of intracellular Ca2+ mobilization. This Ca2+ mobilization is essential to shape Ca2+ signaling in eukaryotic cells. STIM1 is a transmembrane protein located at the endoplasmic reticulum, where it acts as an intraluminal Ca2+ sensor. The transient drop of intraluminal Ca2+ concentration triggers STIM1 activation, which relocates to plasma membrane-endoplasmic reticulum junctions to bind and activate ORAI1, a plasma membrane Ca2+ channel. Thus, the Ca2+ influx pathway mediated by STIM1/ORAI1 is termed store-operated Ca2+ entry (SOCE). STIM and ORAI proteins are also involved in non-SOCE Ca2+ influx pathways, as we discuss here. In this chapter, we review the current knowledge regarding the role of SOCE, STIM1, and ORAI1 in cell signaling, with special focus on the modulation of the activity of kinases, phosphatases, and transcription factors that are strongly influenced by the extracellular Ca2+ influx mediated by these regulators.

**Keywords:** calcium, signaling, SOCE, STIM, ORAI
