Signaling pathways regulating growth and differentiation of adult stem cells

Larry Denner, Margaret Howe, Randall Urban

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

This chapter focuses on signaling pathways that regulate growth and differentiation of adult stem cells. The POU domain containing transcription factor Oct-4, previously known as Oct-3/4, confers ESC self-renewal and pluripotency. As embryonic stem cells (ESC) differentiate and lose pluripotency, expression of Oct-4 is downregulated. Subsequent overexpression allows cells to regain the ESC primitive phenotype, indicating this marker alone can reprogram self-renewal mechanisms. Oct-4 is composed of two isoforms, Oct-4 A and Oct-4B. These have identical central POU DNA binding domains and C-terminal domains, but differ in the N-terminal domains. The A isoform resides in the nucleus, possesses a functional N-terminal transactivation domain, and induces target gene expression, while the B isoform is cytoplasmic and has no transactivation domain. Signaling of the Wnt pathway is regulated by interactions between several key proteins, including glycogen synthase kinase-3β (GSK-3'), β-catenin, and T cell factor-4 (Tcf-4). The rate-limiting signaling node in this pathway is GSK-3', a serine-threonine kinase with two isoforms. The alpha isoform (51 kDa) is a key regulator of glucose metabolism, while the beta form (47 kDa) mediates Wnt signaling through β-catenin. The kinase activity of glycogen synthase kinase (GSK)-3' is regulated by phosphorylation on Tyr216 and Ser9. Tyr216 phosphorylation increases the kinase catalytic activity of GSK-3', while phosphorylation of Ser9 decreases GSK-3' activity. GSK-3' has a role in a wide variety of disease processes so it has been a key target for drug discovery efforts that have produced more than 30 small molecule inhibitors of GSK-3' with different ranges of specificity.

Original languageEnglish (US)
Title of host publicationHandbook of Cell Signaling, 2/e
PublisherElsevier Inc.
Pages2743-2751
Number of pages9
Volume3
ISBN (Print)9780123741455
DOIs
StatePublished - 2010

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Glycogen Synthase Kinase 3
Adult Stem Cells
Stem cells
Protein Isoforms
Phosphorylation
Growth
Embryonic Stem Cells
Catenins
Transcriptional Activation
Transcription Factor 7-Like 2 Protein
Octamer Transcription Factor-3
Phosphotransferases
Regain
Wnt Signaling Pathway
Protein-Serine-Threonine Kinases
Drug Discovery
Metabolism
Gene expression
Catalyst activity
Down-Regulation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Signaling pathways regulating growth and differentiation of adult stem cells. / Denner, Larry; Howe, Margaret; Urban, Randall.

Handbook of Cell Signaling, 2/e. Vol. 3 Elsevier Inc., 2010. p. 2743-2751.

Research output: Chapter in Book/Report/Conference proceedingChapter

Denner, Larry ; Howe, Margaret ; Urban, Randall. / Signaling pathways regulating growth and differentiation of adult stem cells. Handbook of Cell Signaling, 2/e. Vol. 3 Elsevier Inc., 2010. pp. 2743-2751
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