title: The regulation of STIM1 by phosphorylation.
abstract: Calcium ion (Ca(2+)) concentration plays a key role in cell signaling in eukaryotic cells. At the cellular level, Ca(2+) directly participates in such diverse cellular events as adhesion and migration, differentiation, contraction, secretion, synaptic transmission, fertilization, and cell death. As a consequence of these diverse actions, the cytosolic concentration of free Ca(2+) is tightly regulated by the coordinated activity of Ca(2+) channels, Ca(2+) pumps, and Ca(2+)-binding proteins. Although many of these regulators have been studied in depth, other proteins have been described recently, and naturally far less is known about their contribution to cell physiology. Within this last group of proteins, STIM1 has emerged as a major contributor to Ca(2+) signaling by means of its activity as Ca(2+) channel regulator. STIM1 is a protein resident mainly, but not exclusively, in the endoplasmic reticulum (ER), and activates a set of plasma membrane Ca(2+) channels termed store-operated calcium channels (SOCs) when the concentration of free Ca(2+) within the ER drops transiently as a result of Ca(2+) release from this compartment. Knowledge regarding the molecular architecture of STIM1 has grown considerably during the last years, and several structural domains within STIM1 have been reported to be required for the specific molecular interactions with other important players in Ca(2+) signaling, such as Ca(2+) channels and microtubules. Within the modulators of STIM1, phosphorylation has been shown to both activate and inactivate STIM1-dependent Ca(2+) entry depending on the cell type, cell cycle phase, and the specific residue that becomes modified. Here we shall review current knowledge regarding the modulation of STIM1 by phosphorylation.
authors: Department of Biochemistry and Molecular Biology; School of Life Sciences; University of Extremadura; Badajoz, Spain.
authors: Eulalia
authors: E
authors: Pozo-Guisado
authors: Department of Biochemistry and Molecular Biology; School of Life Sciences; University of Extremadura; Badajoz, Spain.
authors: Francisco Javier
authors: FJ
authors: Martin-Romero
keywords: Calcium signaling; EB1; ORAI1; STIM1; microtubules; phosphorylation; store-operated calcium entry