Article
- The EMBO Journal (2007) 26, 3957 - 3967
- doi:10.1038/sj.emboj.7601818
Published online: 2 August 2007
Subject Category:
TGF-
activates Erk MAP kinase signalling through direct phosphorylation of ShcA
Matt K Lee1, Cécile Pardoux2, Marie C Hall2, Pierre S Lee2, David Warburton3, Jing Qing2, Susan M Smith1 and Rik Derynck2
- Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA, USA
- Programs in Cell Biology and Developmental Biology, Department of Cell and Tissue Biology and Anatomy, University of California, San Francisco, CA, USA
- Saban Research Institute, Childrens Hospital Los Angeles, University of Southern California, CA, USA
Correspondence to:
Matt K Lee, Center for Craniofacial Molecular Biology, University of Southern California, 2250 Alcazar Street, CSA-103, Los Angeles, CA 90033, USA. Tel.: +1 323 442 3805; Fax: +1 323 442 2981; E-mail: mattlee@usc.edu
Received 20 March 2007; Accepted 12 July 2007
Abstract
Erk1/Erk2 MAP kinases are key regulators of cell behaviour and their activation is generally associated with tyrosine kinase signalling. However, TGF-
stimulation also activates Erk MAP kinases through an undefined mechanism, albeit to a much lower level than receptor tyrosine kinase stimulation. We report that upon TGF- stimulation, the activated TGF- type I receptor (TRI) recruits and directly phosphorylates ShcA proteins on tyrosine and serine. This dual phosphorylation results from an intrinsic TRI tyrosine kinase activity that complements its well-defined serine-threonine kinase function. TGF--induced ShcA phosphorylation induces ShcA association with Grb2 and Sos, thereby initiating the well-characterised pathway linking receptor tyrosine kinases with Erk MAP kinases. We also found that TRI is tyrosine phosphorylated in response to TGF-. Thus, TRI, like the TGF- type II receptor, is a dual-specificity kinase. Recruitment of tyrosine kinase signalling pathways may account for aspects of TGF- biology that are independent of Smad signalling.
Keywords:
- Erk,
- MAP kinase,
- receptor,
- ShcA/TGF-
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