Functional characterization of protein kinase c beta 1 in self-renewal
Studies on the activation mechanisms of MMP-2 and ADAM17: identification of regula...
Mecanisms of regulation of the expression of the atypical protein kinase C PKMz an...
Grant number: | 12/17279-5 |
Support Opportunities: | Scholarships in Brazil - Scientific Initiation |
Start date: | November 01, 2012 |
End date: | October 31, 2014 |
Field of knowledge: | Biological Sciences - Biochemistry - Molecular Biology |
Principal Investigator: | Deborah Schechtman |
Grantee: | Gabriela Ávila de Grazia |
Host Institution: | Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
Abstract Embryonic stem cells (ESC) proliferate while retaining the ability to differentiate into different cell types. For them to be efficiently used in cellular therapies for tissue replacement, it is necessary to understand the molecular processes that lead to differentiation and self-renewal of ESC. Protein kinase C (PKC) is composed of a family of ten isozymes capable of phosphorylating serines and threonines. These kinases are involved in diverse cellular functions such as proliferation, differentiation, carcinogenesis, angiogenesis, and drug resistance among others. The functions of each isoenzyme mainly depend on their subcellular location and requirements for activation. However, the exact function of each isoform is still unclear, because for a long time it had no isoform-specific inhibitors. In recent years our laboratory has characterized the role of different isozymes of PKCs in ESC as undifferentiated. Our data show that PKC²I is the isoform predominantly present in the nucleus of undifferentiated ESC. Lower molecular weight forms of this isoenzyme are found in undifferentiated ESC core. Yet, fosfoproteomics studies indicate that most substrates PKC²I in ESC are undifferentiated nuclear proteins that regulate the transcription of proteins involved in processes of proliferation/differentiation. During differentiation we also note a change in subcellular localization of PKC²I which becomes expressed in the cytoplasm of various differentiated cells, and that some differentiated cells fail to express PKC²I. Together, these data contribute to the hypothesis that PKC²I is involved in key processes of undifferentiated ESC, for example, maintaining its undifferentiated state. Thus, this project aims to evaluate the function of PKC²I through the identification of partner proteins that interact with this isoform in undifferentiated murine ESC, thus contributing to the elucidation of signaling cascades that lead to self-renewal of ESC. (AU) | |
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