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PKC and signal transduction pathways of self-renewal and differentiation in murine embryonic stem cells

Grant number: 10/18640-8
Support type:Regular Research Grants
Duration: April 01, 2011 - August 31, 2013
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Deborah Schechtman
Grantee:Deborah Schechtman
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Embryonic stem cells (ESC) proliferate indefinitely maintaining their capacity to differentiate in several cell types (self-renewal). For the efficient use of ESC in cell therapy we need to understand specific molecular processes of differentiation and self-renewal of ESC. In the last years our laboratory has characterized the role of different isoenzymes of Protein kinase C (PKCs) in undifferentiated ESCs. Amongst the isoenzymes expressed in ESCs, lower molecular weight forms of PKC²I (possibly catalytically active enzyme) are expressed in the nucleus of murine ESCs. Additionally we observed that upon differentiation there is a change in the subcellular localization of PKCbI which is found in the cytoplasm of several cells, and some no longer express PKCbI. Besides that, our phosphoproteomics studies indicate that most of the PKCBI substrates in undifferentiated ESCS are nuclear proteins that regulate transcription of proteins involved in proliferation/ differentiation processes. Taken together, our data contributes to the hypothesis that PKCbI could be involved in important processes of undifferentiated ESCs, such as the maintenance of the undifferentiated state. We also saw that PKCdelta is involved in proliferation of undifferentitated ESCs via MAPK activation and that PKCzeta/lambda participate in cytoskeleton remodeling processes and possibly in cell/cell adhesion of undifferentiated ESCs. To this end in the present project we wish to continue our previous studies characterizing signal transduction pathways of PKC betaI, delta and zeta/lambda and the importance of these isonezymes for ESC self-renewal and early differentiation processes. (AU)

Articles published in Agência FAPESP Newsletter about the research grant
Study helps to understand how the protein ‘on/off switch’ works 
Articles published in Pesquisa FAPESP Maganize about the research grant:
Molecular origami 

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DUARTE, MARIANA LEMOS; PENA, DARLENE APARECIDA; NUNES FERRAZ, FELIPE AUGUSTO; BERTI, DENISE APARECIDA; PASCHOAL SOBREIRA, TIAGO JOSE; COSTA-JUNIOR, HELIO MIRANDA; ABDEL BAQUI, MUNIRA MUHAMMAD; DISATNIK, MARIE-HELENE; XAVIER-NETO, JOSE; LOPES DE OLIVEIRA, PAULO SERGIO; SCHECHTMAN, DEBORAH. Protein folding creates structure-based, noncontiguous consensus phosphorylation motifs recognized by kinases. Science Signaling, v. 7, n. 350 NOV 4 2014. Web of Science Citations: 24.
GARAVELLO, NICOLE MILARE; PENA, DARLENE APARECIDA; CAMARGO BONATTO, JOSE MATHEUS; DUARTE, MARIANA LEMOS; COSTA-JUNIOR, HELIO MIRANDA; SCHUMACHER, ROBERT IVAN; FORTI, FABIO LUIS; SCHECHTMAN, DEBORAH. Activation of protein kinase C delta by psi delta RACK peptide promotes embryonic stem cell proliferation through ERK 1/2. JOURNAL OF PROTEOMICS, v. 94, p. 497-512, DEC 6 2013. Web of Science Citations: 5.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.