Survival of the weakest: signaling aided by endosomes.
The tyrosine kinase receptor c-Met plays a key role in cell proliferation, morphogenesis, and motility in response to hepatocyte growth factor. C-Met is often altered in cancer and is a major target for therapeutic intervention. Despite knowing a great deal of the molecular machinery downstream of this receptor tyrosine kinase, the spatiotemporal regulation of c-Met signaling still remains elusive. In this issue of the Journal of Cell Biology, Kermorgant and Parker (Kermorgant, S. and P.J. Parker. 2008. J. Cell Biol. 182:855-863) provide evidence for a model in which the c-Met-activated STAT3 signal is mediated by endosomal trafficking. This study elegantly highlights how weak signals can be effectively transmitted to the nucleus by exploiting endosomal compartments, raising important mechanistic implications for the signaling research community.
McShane
Marisa P
MP
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Zerial
Marino
M
D011992:Endosomes / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D021381:Protein Transport; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D019859:Proto-Oncogene Proteins c-met
Nat Cell Biol. 2007 Mar;9(3):324-30
17310240
EMBO J. 2004 Oct 1;23(19):3721-34
15385963
J Cell Biol. 2008 Sep 8;182(5):855-63
18779368
Nature. 1998 Jan 15;391(6664):285-8
9440692
J Biol Chem. 2003 Aug 1;278(31):28921-9
12716900
Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8150-5
15919823
Cell. 2008 Jul 11;134(1):135-47
18614017
Dev Cell. 2007 Sep;13(3):377-90
17765681
J Cell Biol. 2001 Feb 19;152(4):765-76
11266467
EMBO J. 2002 Jul 1;21(13):3255-63
12093727
Mol Syst Biol. 2007;3:144
18004277
J Cell Biol. 2006 Jan 16;172(2):245-57
16401721
Cell. 2004 Feb 6;116(3):445-56
15016378
Mol Biol Cell. 2003 Apr;14(4):1346-54
12686592
Eur J Cell Biol. 2007 Sep;86(9):533-47
17583371
J Biol Chem. 2006 Mar 17;281(11):7302-8
16407171
Mol Cell Biol. 2006 Dec;26(23):8928-41
17000777
Nat Cell Biol. 2006 May;8(5):516-23
16622416
Cell. 2008 May 2;133(3):486-97
18455989
Nat Rev Drug Discov. 2008 Jun;7(6):504-16
18511928
Nat Rev Mol Cell Biol. 2003 Dec;4(12):915-25
14685170