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New functional complexes deriving from the interaction of Gαq with proteins that contain PB1 domains, and the possible repercussion of this in cardiovascular pathologies

Lead Researcher:
Catalina Ribas Núñez

Research Centre:
Centro de Biología Molecular Severo Ochoa. CSIC-UAM.

Abstract: 

Catalina Ribas N¡§²ñezReceptors bound to G proteins (GPCR) mediate the actions of several messengers which play an essential role in the functioning and dysfunctions of the cardiovascular system. These receptors regulate a broadly interconnected network of biochemical routes, including the control of activity by members of the MAPKs (mitogen-activated protein kinases) family, which are extremely important in cardiovascular pathologies. Our group recently described a new signalling pathway in the context of GPCR bound to Gqproteins that may form a part of a new Gαq interactome. These previous results indicate that there is a functional interaction between Gαq and PKCζ, identifying this kinase as a new Gαq effector, and showing that activation of this pathway seems to be important for the development of cardiac hypertrophy. In this context, our aims are: 1) To characterise the functional repercussions deriving from the activation of the Gαq-PKCζ pathway and that of the Gαq interactome with other proteins such as PKCζ which possess PB1 domains, such as p62/SQTSM1,and 2) To determine the possible involvement of this pathway in cell death processes, autophagy and oxidative stress, as well as in the development of cardiovascular diseases. Knowledge of these new signalling pathways and their mechanisms of regulation in cardiac pathologies is essential to explain variations observed in different cardiomyopathologies of different types, thereby making it possible to develop new diagnostic and therapeutic strategies.


Researcher's web address:
http://web4.cbm.uam.es/joomla-rl/index.php/es/index.php?option=com_content&view=article&id=348



Catalina Ribas Núñez

She is currently Tenured Professor in the Molecular Biology Department of the Universidad Autónoma de Madrid. Her research group is in the Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM) and is a member of the Fundación de Investigación Biomédica La Princesa. She has wide experience in the field of signalling and regulation of receptors that are bound to G proteins (GPCR). The interest of her research team centres on the study of the mechanisms of action of GPCRs, under normal as well as pathological circumstances. Dr. Catalina Ribas has used different pharmacological, biochemical and molecular biology techniques to study the regulatory mechanisms of the GPCRs transduction system. During her postdoctoral visit to the Medical University of South Carolina (USA) she took part in the identification, characterisation and purification of proteins that play a role in the signal transduction complex, which act at G proteins level and form part of the multimolecular signal of transduction complex of the receptors bound to these proteins.

Following her return to Spain, Dr. Ribas continued working on receptors bound to G proteins and their regulation by kinases bound to these receptors (GRKs), as well as the interaction of these pathways with those of MAPKs signalling pathways. Specifically, she centres her research on the processes which are dependent on the activation of receptors bound to Gq for which the corresponding effector has yet to be found. Her results suggest the existence of a functional interaction between Gαq and PKCz which seems to play an important role in the development of cardiac hypertrophy. Dr. Ribas' group has therefore described a new adaptor role for Gαq, and its main aim now is to characterise this new functional interaction in depth, determining its role in other signalling pathways, as well as in other cell functions connected with the activation of GPCRs bound to Gαq, together with its possible modulation by proteins which regulate signalling mediated by these G proteins (GRKs, Ric8, RGS, EBP50).


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