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SMAD phosphorylation and the TGF-beta pathway

Published on November 30, 2010   58 min

A selection of talks on Biochemistry

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0:00
Hello. Welcome to the lecture on SMAD Phosphorylation and the TGF-β Pathway. This is your host Joan Massagué.
0:10
The human genome encodes about 500 different protein kinases. Of these, close to 100 are tyrosine (tyr) kinases, of which about half serve as receptors for growth factors. They are transmembrane tyrosine kinases. The rest, the majority are serine/threonine kinases and only a few of these are in fact transmembrane receptors. A majority of these receptors form a family shown as a single branch in the human kinome map and this family all of its members serve as receptors for a very important family of cytokines which is the TGFβ family.
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TGFβ is the acronym for transforming growth factor beta, a cytokine, and the founding member of a large family of factors, more than 30, encoded in the human genome. Factors that play pivotal roles in many aspects of embryo development as well as tissue maintenance or homeostasis. TGFβ and its family members are a paradigm of multifunctionality in biology. For example, TGFβ activin and nodal as well as the related bone morphogenetic proteins or BMPs play very important roles in laying down the symmetry axis in early embryo development. Anterior-posterior, left-right, and dorsoventral axis. Yet, later in development, these factors can play important roles in negatively controlling cell growth and tissue growth. The relative of TGFβ, known as myostatin, is an important suppressor of skeletal muscle development. Mutations that inactivate the myostatin pathway give rise to excessive skeletal tissue mass, as in for example, in certain breeds of cattle developed for this purpose. The multifunctionality of these factors also becomes evident in disease. For example, TGFβ, which is normally a powerful inhibitor of a number of epithelial tissues and their growth can become a strong promoter of epithelial cancers or carcinomas especially during the metastatic phase the spread of these tumors to the bone. As we see in this example, cancer cells are acting to destroy the bone matrix and TGFβ released from the bone matrix can act in turn on the cancer cells to further promote their action and the destruction of the bone through the outgrowth of metastasis. How cells respond to

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SMAD phosphorylation and the TGF-beta pathway

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