Skip to main content
SpringerLink
Log in

Protein Kinase C Signaling in Embryonic Stem Cell Self Renewal and Cardiac Differentiation

  • Chapter
  • First Online:
Stem Cells and Cancer Stem Cells, Volume 9

Part of the book series: Stem Cells and Cancer Stem Cells ((STEM,volume 9))

  • 1389 Accesses

Abstract

Embryonic stem cells (ESC); proliferate while maintain the ability to differentiate into several cell types (self-renewal). For the efficient use of ESC in cell therapies it is necessary to characterize the specific signaling pathways that lead to ESC differentiation, proliferation and self-renewal. The Protein kinase C (PKC) family of serine/threonine kinases has been identified as key enzymes for the processes of proliferation and differentiation of ESCs to cardiomyocytes however, the exact function of each PKC isoenzyme remains unclear, and this is partially due to the conserved nature of these kinases and the fact that specific modulators have only recently become available. In the present chapter we discuss recent studies describing the function PKC isoenzymes in murine ESC proliferation, self renewal and cardiac-differentiation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Bandyopadhyay G, Standaert ML, Sajan MP, Kanoh Y, Miura A, Braun U, Kruse F, Leitges M, Farese RV (2004) Protein kinase C-lambda knockout in embryonic stem cells and adipocytes impairs insulin-stimulated glucose transport. Mol Endocrinol 18:373–383

    Article  PubMed  CAS  Google Scholar 

  • Bekhite MM, Finkensieper A, Binas S, Muller J, Wetzker R, Figulla HR, Sauer H, Wartenberg M (2011) VEGF-mediated PI3K class IA and PKC signaling in cardiomyogenesis and vasculogenesis of mouse embryonic stem cells. J Cell Sci 124:1819–1830

    Article  PubMed  CAS  Google Scholar 

  • Boheler KR, Czyz J, Tweedie D, Yang HT, Anisimov SV, Wobus AM (2002) Differentiation of pluripotent embryonic stem cells into cardiomyocytes. Circ Res 91:189–201

    Article  PubMed  CAS  Google Scholar 

  • Burridge PW, Keller G, Gold JD, Wu JC (2012) Production of de novo cardiomyocytes: human pluripotent stem cell differentiation and direct reprogramming. Cell Stem Cell 10:16–28

    Article  PubMed  CAS  Google Scholar 

  • Cho Y, Klein MG, Talmage DA (1998) Distinct functions of protein kinase Calpha and protein kinase Cbeta during retinoic acid-induced differentiation of F9 cells. Cell Growth Differ 9:147–154

    PubMed  CAS  Google Scholar 

  • Costa-Junior HM, Garavello NM, Duarte ML, Berti DA, Glaser T, Andrade AD, Labate CA, Ferreira AT, Perales JE, Xavier-Neto J, Krieger JE, Schechtman D (2010) Phosphoproteomics profiling suggests a role for nuclear betaIotaPKC in transcription processes of undifferentiated murine embryonic stem cells. J Proteome Res 9:6191–6206

    Article  PubMed  CAS  Google Scholar 

  • Dard N, Le T, Maro B, Louvet-Vallee S (2009) Inactivation of aPKClambda reveals a context dependent allocation of cell lineages in preimplantation mouse embryos. PLoS One 4:e7117

    Article  PubMed  Google Scholar 

  • Dehghani H, Hahnel AC (2005) Expression profile of protein kinase C isozymes in preimplantation mouse development. Reproduction 130:441–51

    Article  PubMed  CAS  Google Scholar 

  • Dell’era P, Ronca R, Coco L, Nicoli S, Metra M, Presta M (2003) Fibroblast growth factor receptor-1 is essential for in vitro cardiomyocyte development. Circ Res 93:414–420

    Article  PubMed  Google Scholar 

  • Dutta D, Ray S, Home P, Larson M, Wolfe MW, Paul S (2011) Self-renewal versus lineage commitment of embryonic stem cells: protein kinase C signaling shifts the balance. Stem Cells 29:618–628

    Article  PubMed  CAS  Google Scholar 

  • Heo JS, Han HJ (2006) ATP stimulates mouse embryonic stem cell proliferation via protein kinase C, phosphatidylinositol 3-kinase/Akt, and mitogen-activated protein kinase signaling pathways. Stem Cells 24:2637–2648

    Article  PubMed  CAS  Google Scholar 

  • Heo JS, Lee YJ, Han HJ (2006) EGF stimulates proliferation of mouse embryonic stem cells: involvement of Ca2+ influx and p44/42 MAPKs. Am J Physiol Cell Physiol 290:C123–33

    Article  PubMed  CAS  Google Scholar 

  • Heo JS, Lee MY, Han HJ (2007) Sonic hedgehog stimulates mouse embryonic stem cell proliferation by cooperation of Ca2+/protein kinase C and epidermal growth factor receptor as well as Gli1 activation. Stem Cells 25:3069–80

    Article  PubMed  CAS  Google Scholar 

  • Ieda M, Fu JD, Delgado-Olguin P, Vedantham V, Hayashi Y, Bruneau BG, Srivastava D (2010) Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell 142:375–386

    Article  PubMed  CAS  Google Scholar 

  • Kapur N, Mignery GA, Banach K (2007) Cell cycle-dependent calcium oscillations in mouse embryonic stem cells. Am J Physiol Cell Physiol 292:C1510–c1518

    Article  PubMed  CAS  Google Scholar 

  • Kim YH, Han HJ (2008) Synergistic effect of high glucose and ANG II on proliferation of mouse embryonic stem cells: involvement of PKC and MAPKs as well as AT1 receptor. J Cell Physiol 215:374–382

    Article  PubMed  CAS  Google Scholar 

  • Kim MH, Kim MO, Kim YH, Kim JS, Han HJ (2009) Linoleic acid induces mouse embryonic stem cell proliferation via Ca2+/PKC, PI3K/Akt, and MAPKs. Cell Physiol Biochem 23:53–64

    Article  PubMed  CAS  Google Scholar 

  • Kim MO, Lee YJ, Han HJ (2010a) Involvement of Cx43 phosphorylation in 5’-N-ethylcarboxamide-induced migration and proliferation of mouse embryonic stem cells. J Cell Physiol 224:187–194

    PubMed  CAS  Google Scholar 

  • Kim YH, Ryu JM, Lee YJ, Han HJ (2010b) Fibronectin synthesis by high glucose level mediated proliferation of mouse embryonic stem cells: involvement of ANG II and TGF-beta1. J Cell Physiol 223:397–407

    PubMed  CAS  Google Scholar 

  • Lee SH, Na SI, Heo JS, Kim MH, Kim YH, Lee MY, Kim SH, Lee YJ, Han HJ (2009) Arachidonic acid release by H2O2 mediated proliferation of mouse embryonic stem cells: involvement of Ca2+/PKC and MAPKs-induced EGFR transactivation. J Cell Biochem 106:787–797

    Article  PubMed  CAS  Google Scholar 

  • Lee HJ, Jeong CH, Cha JH, Kim KW (2010) PKC-delta inhibitors sustain self-renewal of mouse embryonic stem cells under hypoxia in vitro. Exp Mol Med 42:294–301

    Article  PubMed  CAS  Google Scholar 

  • Mauritz C, Schwanke K, Reppel M, Neef S, Katsirntaki K, Maier LS, Nguemo F, Menke S, Haustein M, Hescheler J, Hasenfuss G, Martin U (2008) Generation of functional murine cardiac myocytes from induced pluripotent stem cells. Circulation 118:507–517

    Article  PubMed  Google Scholar 

  • Mobley S, Shookhof JM, Foshay K, Park M, Gallicano GI (2010) PKG and PKC are down-regulated during cardiomyocyte differentiation from embryonic stem cells: manipulation of these pathways enhances cardiomyocyte production. Stem Cells Int 2010:701212

    PubMed  Google Scholar 

  • Mochly-Rosen D (1995) Localization of protein kinases by anchoring proteins: a theme in signal transduction. Science 268:247–51

    Article  PubMed  CAS  Google Scholar 

  • Moscat J, Diaz-Meco MT, Wooten MW (2009) Of the atypical PKCs, Par-4 and p62: recent understandings of the biology and pathology of a PB1-dominated complex. Cell Death Differ 16:1426–37

    Article  PubMed  CAS  Google Scholar 

  • Newton AC (2001) Protein kinase C: structural and spatial regulation by phosphorylation, cofactors, and macromolecular interactions. Chem Rev 101:2353–64

    Article  PubMed  CAS  Google Scholar 

  • Okita K, Ichisaka T, Yamanaka S (2007) Generation of germline-competent induced pluripotent stem cells. Nature 448:313–7

    Article  PubMed  CAS  Google Scholar 

  • Park JH, Lee MY, Heo JS, Han HJ (2008) A potential role of connexin 43 in epidermal growth factor-induced proliferation of mouse embryonic stem cells: involvement of Ca2+/PKC, p44/42 and p38 MAPKs pathways. Cell Prolif 41:786–802

    Article  PubMed  CAS  Google Scholar 

  • Piazzi M, Bavelloni A, Faenza I, Blalock W, Urbani A, D’aguanno S, Fiume R, Ramazzotti G, Maraldi NM, Cocco L (2010) eEF1A phosphorylation in the nucleus of insulin-stimulated C2C12 myoblasts: Ser(3) is a novel substrate for protein kinase C betaI. Mol Cell Proteomics 9:2719–2728

    Article  PubMed  CAS  Google Scholar 

  • Prudhomme W, Daley GQ, Zandstra P, Lauffenburger DA (2004) Multivariate proteomic analysis of murine embryonic stem cell self-renewal versus differentiation signaling. Proc Natl Acad Sci USA 101:2900–2905

    Article  PubMed  CAS  Google Scholar 

  • Quinlan LR, Faherty S, Kane MT (2003) Phospholipase C and protein kinase C involvement in mouse embryonic stem-cell proliferation and apoptosis. Reproduction 126:121–131

    Article  PubMed  CAS  Google Scholar 

  • Schechtman D, Mochly-Rosen D (2001) Adaptor proteins in protein kinase C-mediated signal transduction. Oncogene 20:6339–6347

    Article  PubMed  CAS  Google Scholar 

  • Schratt G, Philippar U, Berger J, Schwarz H, Heidenreich O, Nordheim A (2002) Serum response factor is crucial for actin cytoskeletal organization and focal adhesion assembly in embryonic stem cells. J Cell Biol 156:737–750

    Article  PubMed  CAS  Google Scholar 

  • Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676

    Article  PubMed  CAS  Google Scholar 

  • Van Riggelen J, Yetil A, Felsher DW (2010) MYC as a regulator of ribosome biogenesis and protein synthesis. Nat Rev Cancer 10:301–309

    Article  PubMed  Google Scholar 

  • Ventura C, Zinellu E, Maninchedda E, Fadda M, Maioli M (2003) Protein kinase C signaling transduces endorphin-primed cardiogenesis in GTR1 embryonic stem cells. Circ Res 92:617–622

    Article  PubMed  CAS  Google Scholar 

  • Ying QL, Wray J, Nichols J, Batlle-Morera L, Doble B, Woodgett J, Cohen P, Smith A (2008) The ground state of embryonic stem cell self-renewal. Nature 453:519–523

    Article  PubMed  CAS  Google Scholar 

  • Yun SP, Lee MY, Ryu JM, Han HJ (2009) Interaction between PGE2 and EGF receptor through MAPKs in mouse embryonic stem cell proliferation. Cell Mol Life Sci 66:1603–1616

    Article  PubMed  CAS  Google Scholar 

  • Zeevi-Levin N, Itskovitz-Eldor J, Binah O (2010) Functional properties of human embryonic stem cell-derived cardiomyocytes. Crit Rev Eukaryot Gene Expr 20:51–59

    Article  PubMed  Google Scholar 

  • Zhou X, Quann E, Gallicano GI (2003) Differentiation of nonbeating embryonic stem cells into beating cardiomyocytes is dependent on downregulation of PKC beta and zeta in concert with upregulation of PKC epsilon. Dev Biol 255:407–422

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departmento de Bioquímica, Instituto de Química, Universidade de Sao Paulo, Av. Prof. Lineu Prestes, 748 Sala 1020, Sao Paulo, SP, 05508-000, Brazil

    Deborah Schechtman & Denise Aparecida Berti

Authors
  1. Deborah Schechtman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Denise Aparecida Berti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Deborah Schechtman .

Editor information

Editors and Affiliations

  1. , Kean University, Room 213, Library building, Morris Avenue 1000, Union, 07083, New Jersey, USA

    M.A. Hayat

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Schechtman, D., Berti, D.A. (2013). Protein Kinase C Signaling in Embryonic Stem Cell Self Renewal and Cardiac Differentiation. In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells, Volume 9. Stem Cells and Cancer Stem Cells, vol 9. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5645-8_10

Download citation

Publish with us

Policies and ethics

Search

Navigation