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Biphasic role of TGF‐β1 in signal transduction and crosstalk
Author(s) -
Wenner Charles E.,
Yan Shaochun
Publication year - 2003
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.10243
Subject(s) - microbiology and biotechnology , signal transduction , transforming growth factor , crosstalk , mapk/erk pathway , cell cycle , cell growth , receptor , cell , biology , chemistry , biochemistry , physics , optics
TGF‐β1 induces cell cycle activation in mouse embryonic fibroblasts by down regulation of p27 Kip1 but it can also induce delay of EGF‐induced cell cycle activation in these cells under similar conditions. In an attempt to determine the basis for these responses, the study of early TGF‐β1‐induced signal transduction pathways in the presence and absence of EGF was undertaken. It is proposed that a likely target for the inhibition by TGF‐β1 of the early EGF‐induced p42/p44 MAPK is at the c‐Raf locus. The finding that the catalytic subunits of PKA are associated with Raf‐1 within minutes following application of TGF‐β1 but not EGF in fibroblasts arrested in early G1 is suggestive of a role of PKA‐Raf‐1 interaction in TGF‐β1 induced delay of EGF‐induced cell cycle kinetics. A model for TGF‐β1 induced translocation to the plasma membrane‐associated Raf‐1 is proposed. Reports that Rho‐like GTPase activity is critical for the activation of TGF‐β1 downstream pathways raises the question as to whether Rho proteins are involved in these observed TGF‐β1‐induced responses. Post‐receptor signaling mechanisms for TGF‐β1 and cross‐talk with PKA‐mediated pathways are examined in an effort to explain the modulation by TGF‐β1 of mitogen‐induced cell proliferation in mesenchymal cells. © 2003 Wiley‐Liss, Inc.