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(Circulation Research. 2004;94:1276.)
© 2004 American Heart Association, Inc.

Editorials

Ca²⁺ Control of Transcription

Can We Extrapolate Signaling Cascades From Neurons to Vascular Smooth Muscle Cells?

Gerrit Isenberg

From the Department of Physiology, Martin-Luther University, 06097 Halle, Germany.

Correspondence to Dr Gerrit Isenberg, Department of Physiology, Martin-Luther University, Magdeburger Strasse 6, 06097 Halle, Germany. E-mail gerrit.isenberg@medizin.uni-halle.de

Key Words: vascular myocyte • growth response • [Ca²⁺]_c • CREB • SOCE

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The Ca²⁺ hypothesis of transcription suggests that increments in the cytosolic Ca²⁺ concentration [Ca²⁺]_c can activate transcription. The Ca²⁺ hypothesis has emerged in the field of neurosciences^1,2 and was translated to vascular smooth muscle cells (VSMC) by the Burlington group.^3–5 The article by Pulver et al in this issue⁶ demonstrates a close correlation between the increase in [Ca²⁺]_c, phosphorylation of nuclear CREB, and the expression of c-fos. Pulver et al introduce the idea that transcriptional activation may be regulated by store-operated Ca²⁺ entry (SOCE)^7–9 as it is activated when thapsigargin blocks the Ca²⁺-ATPase SERCA, thereby depleting the SR Ca²⁺ content. The authors demonstrate this thapsigargin effect not only in cultured VSMC but also in VSMC of intact arteries. They conclude that SOCE may activate transcription and may therefore control the differentiated (contractile) or proliferative (secretory) phenotype of VSMC.¹⁰

Ca²⁺-Mediated Phosphorylation of CREB

The Ca²⁺/cAMP response element binding protein CREB is a transcription factor.¹¹ CREB transcriptional activation occurs through its binding to the CREB-binding protein, CBP, a co-activator protein that links to many factors of the general transcriptional machinery. Phosphorylation of CREB at Ser-133 increases its affinity for CBP, and it can be observed with phospho-specific antibodies. CREB can be phosphorylated not only at SER-133 but also at S-142. Phosphorylation is mediated by a variety of kinases, with the cAMP/PKA pathway often being the principal modulator.¹² In the case of Ca²⁺-dependent activation, CREB phosphorylation is thought to result from the following signaling cascade:¹³ Ca²⁺ binds to calmodulin, Ca²⁺/CaM . . . [Full Text of this Article]