Purification and Characterization of Bovine Heart Glycogen Synthase Kinase-3

Henry, Scott P.; Killilea, S.Derek

doi:10.1080/10826069408010098

Cited by 1 publication

(1 citation statement)

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“…15,17 Kinase activities of GSK-3␣ and GSK-3␤ are regulated similarly in some cases 18 but differently in other cases. 19,20 Although both isoforms are expressed in the heart, 21 most studies that have been conducted thus far have examined the role of GSK-3␤, possibly because of the general lack of specific reagents for GSK-3␣. Although GSK-3␤ was initially described for its function to inhibit glycogen synthesis through phosphorylation of glycogen synthase, 22,23 it has been revealed that GSK-3␤ regulates a wide range of cellular functions, including metabolism, gene expression, and cytoskeletal integrity 13 ( Figure 1).…”

Section: Gsk-3␤ Is a Proline-directed Serine/threoninementioning

confidence: 99%

Glycogen Synthase Kinase-3β

Hardt¹,

Sadoshima²

2002

Circulation Research

357

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Abstract-Glycogen synthase kinase-3␤ (GSK-3␤) is a ubiquitously expressed constitutively active serine/threonine kinase that phosphorylates cellular substrates and thereby regulates a wide variety of cellular functions, including development, metabolism, gene transcription, protein translation, cytoskeletal organization, cell cycle regulation, and apoptosis. The activity of GSK-3␤ is negatively regulated by protein kinase B/Akt and by the Wnt signaling pathway. Increasing lines of evidence show that GSK-3␤ is an essential negative regulator of cardiac hypertrophy and that the inhibition of GSK-3␤ by hypertrophic stimuli is an important mechanism contributing to the development of cardiac hypertrophy. GSK-3␤ also plays an important role in regulating cardiac development. In this review, the role of GSK-3␤ in cardiac hypertrophy and development and the potential underlying mechanisms are discussed. Key Words: glycogen synthase kinase-3␤ Ⅲ hypertrophy Ⅲ development Ⅲ Akt Ⅲ Wnt pathway T he signaling mechanisms leading to cardiac hypertrophy have been intensively investigated over the past decade. 1-4 Identification of the signaling molecules necessary for the development of cardiac hypertrophy might lead to the development of therapeutic strategies to prevent or reverse the disease. During the past few years, mitogen-activated protein kinases (MAPKs), calcineurin (a Ca 2ϩ /calmodulindependent protein phosphatase), and Ca 2ϩ /calmodulindependent protein kinases have been intensively investigated because they positively regulate cardiac hypertrophy (see reviews 5,6 ). Equally important in exploring the signaling mechanisms promoting hypertrophy is the dissection of pathways counteracting these prohypertrophic signaling mechanisms, which thereby alleviates the hypertrophic responses. Accumulating evidence suggests that glycogen synthase kinase-3␤ (GSK-3␤) negatively regulates cardiac hypertrophy and that the inhibition of GSK-3␤ by hypertrophic stimuli is an important mechanism in the stimulation of cardiac hypertrophy. 7-12 GSK-3␤ also regulates cardiac development through its effect on Wnt signaling. In the present article, it is our goal to review recent findings regarding the role of GSK-3␤ in cardiac hypertrophy and development and to discuss the potential underlying mechanisms.

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