Wednesday, 12th December 2018
Cell Biology and Immunology
G protein-coupled receptor networks: signal transduction and pathophysiological implications

 

 


Grupo-400

 


Federico Mayor Jr.

ASciStaff

APublications

 

Research summary:

Our laboratory is investigating key nodes in signalling networks involved in prevalent age-related pathologies such as metabolic/cardiovascular diseases and cancer. The GRK2 kinase is one of those key signalling hubs. In addition to its canonical role as a regulator of G protein-coupled receptors (GPCR), GRK2 can also impact cell signalling networks by directly interacting and/or phosphorylating non-GPCR components of Federico Mayor Fig1transduction cascades (such as HDAC6, IRS1, PI3K, EPAC, Mdm2, Smads or p38 Mapk). Such integrated interactions underlie the participation of GRK2 in the control of cell migration, angiogenesis or insulin resistance (IR).

GRK2 levels/activity are altered in human pathologies such as cancer, inflammation and cardiovascular/ metabolic diseases related to IR. We seek to understand how concurrent changes in GRK2 levels (involving different cell types and tissues) integrate at the cellular and organism level, and how they can foster disease progression, by using cellular and animal models (including hemizygous, conditional and tissue-specific GRK2-deficient animals).

We investigate how changes in GRK2 expression in different tumor cell types (tumoral, macrophages and endothelial cells) might act synergistically to promote different aspects of tumor progression (proliferation, survival, senescence, genomic stability, angiogenesis, metastatic invasion) by modulating either GPCRs, the HDAC6 or the Mdm2/p53 sFederico Mayor Fig2ignaling axis, among others.

On the other hand, we analyzwe the GRK2 hub as a central integrator of signaling cascades relevant to IR-related pathologies and co-morbidities in different tissues and cell types (adipose, liver, pancreas, heart, macrophages/immune cells), by simultaneously modulating both the insulin cascade and key GPCRs controlling metabolic homeostasis, nutrient sensing or insulin secretion/sensitivity.

Other signaling node related to GRK2 is Gαq. We have unveiled novel interactions of Gαq with PB1-domain containing proteins such as PKCζ, and we are investigating the functional impact of this new Gαq interactome in cell death, autophagy and oxidative stress processes and in the development of cardiovascular diseases.

 


 

Patents:

  • New phosphorylation site of mitogen-activated protein kinases, modified proteins and applications EP 1899461B1 /WO 2007/028430 Awarded 2010
  • p38 inhibitor peptides and applications. PCT/ES2011/070774.
  • Protection of the effects of p38 inhibitory compounds. PCT/ES2012/070762

NOTE! This site uses cookies and similar technologies.

If you not change browser settings, you agree to it. Learn more

I understand

COOKIES POLICY

What are cookies?

A cookie is a file that is downloaded to your computer when you access certain web pages. Cookies allow a web page, among other things, to store and retrieve information about the browsing habits of a user or their equipment and, depending on the information they contain and the way they use their equipment, they can be used to recognize the user.

Types of cookies

Classification of cookies is made according to a series of categories. However, it is necessary to take into account that the same cookie can be included in more than one category.

  1. Cookies according to the entity that manages them

    Depending on the entity that manages the computer or domain from which the cookies are sent and treat the data obtained, we can distinguish:

    • Own cookies: those that are sent to the user's terminal equipment from a computer or domain managed by the editor itself and from which the service requested by the user is provided.
    • Third party cookies: those that are sent to the user's terminal equipment from a computer or domain that is not managed by the publisher, but by another entity that processes the data obtained through the cookies. When cookies are installed from a computer or domain managed by the publisher itself, but the information collected through them is managed by a third party, they cannot be considered as own cookies.

  2. Cookies according to the period of time they remain activated

    Depending on the length of time that they remain activated in the terminal equipment, we can distinguish:

    • Session cookies: type of cookies designed to collect and store data while the user accesses a web page. They are usually used to store information that only is kept to provide the service requested by the user on a single occasion (e.g. a list of products purchased).
    • Persistent cookies: type of cookies in which the data is still stored in the terminal and can be accessed and processed during a period defined by the person responsible for the cookie, which can range from a few minutes to several years.

  3. Cookies according to their purpose

    Depending on the purpose for which the data obtained through cookies are processed, we can distinguish between:

    • Technical cookies: those that allow the user to navigate through a web page, platform or application and the use of different options or services that exist in it, such as controlling traffic and data communication, identifying the session, access to restricted access parts, remember the elements that make up an order, perform the purchase process of an order, make a registration or participation in an event, use security elements during navigation, store content for the broadcast videos or sound or share content through social networks.
    • Personalization cookies: those that allow the user to access the service with some predefined general characteristics based on a series of criteria in the user's terminal, such as the language, the type of browser through which the user accesses the service, the regional configuration from where you access the service, etc.
    • Analytical cookies: those that allow the person responsible for them to monitor and analyse the behaviour of the users of the websites to which they are linked. The information collected through this type of cookies is used in the measurement of the activity of the websites, applications or platforms, and for the elaboration of navigation profiles of the users of said sites, applications and platforms, in order to introduce improvements in the analysis of the data of use made by the users of the service.

Cookies used on our website

The CBMSO website uses Google Analytics. Google Analytics is a simple and easy to use tool that helps website owners to measure how users interact with the content of the site. You can consult more information about the cookies used by Google Analitycs in this link.

Acceptance of the Cookies Policy

The CBMSO assumes that you accept the use of cookies if you continue browsing, considering that it is a conscious and positive action from which the user's consent is inferred. In this regard, you are previously informed that such behaviour will be interpreted that you accept the installation and use of cookies.

Knowing this information, it is possible to carry out the following actions:

How to modify the configuration of cookies

Using your browser you can restrict, block or delete cookies from any web page. In each browser the process is different, here we show you links on this particular of the most used browsers: