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TGF‐β activates Erk MAP kinase signalling through direct phosphorylation of ShcA
Author(s) -
Lee Matt K,
Pardoux Cécile,
Hall Marie C,
Lee Pierre S,
Warburton David,
Qing Jing,
Smith Susan M,
Derynck Rik
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601818
Subject(s) - biology , receptor tyrosine kinase , microbiology and biotechnology , map kinase kinase kinase , mitogen activated protein kinase , tyrosine phosphorylation , grb2 , phosphorylation , tyrosine kinase , mapk14 , mapk7 , mitogen activated protein kinase kinase , sh2 domain , protein tyrosine phosphatase , kinase , cancer research , signal transduction , mapk/erk pathway , protein kinase a
Erk1/Erk2 MAP kinases are key regulators of cell behaviour and their activation is generally associated with tyrosine kinase signalling. However, TGF‐β 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‐β stimulation, the activated TGF‐β type I receptor (TβRI) recruits and directly phosphorylates ShcA proteins on tyrosine and serine. This dual phosphorylation results from an intrinsic TβRI tyrosine kinase activity that complements its well‐defined serine‐threonine kinase function. TGF‐β‐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 TβRI is tyrosine phosphorylated in response to TGF‐β. Thus, TβRI, like the TGF‐β type II receptor, is a dual‐specificity kinase. Recruitment of tyrosine kinase signalling pathways may account for aspects of TGF‐β biology that are independent of Smad signalling.