Functional and differential proteomic analyses to identify platelet derived factors affecting ex vivo expansion of mesenchymal stromal cells.
Authors: Kinzebach S, Dietz L, Kluter H, Thierse H, Bieback K
BMC Cell Biol, 2013;14(0):48.
Species: Human
Sample Type: whole cells
Application: Flow
Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay.
Authors: Baccelli I, Schneeweiss A, Riethdorf S, Stenzinger A, Schillert A, Vogel V, Klein C, Saini M, Bauerle T, Wallwiener M, Holland-Letz T, Hofner T, Sprick M, Scharpff M, Marme F, Sinn H, Pantel K, Weichert W, Trumpp A
Nat Biotechnol, 2013;31(6):539-44.
Species: Human
Sample Type: whole cells
Application: Flow

HGF R, also known as Met (from N-methyl-N’-nitro-N-nitrosoguanidine induced), is a glycosylated receptor tyrosine kinase that plays a central role in epithelial morphogenesis and cancer development. HGF R is synthesized as a single chain precursor which undergoes cotranslational proteolytic cleavage. This generates a mature HGF R that is a disulfide-linked dimer composed of a 50 kDa extracellular alpha chain and a 145 kDa transmembrane beta chain (1, 2). The extracellular domain (ECD) contains a seven bladed beta -propeller sema domain, a cysteine-rich PSI/MRS, and four Ig-like E-set domains, while the cytoplasmic region includes the tyrosine kinase domain (3, 4). Proteolysis and alternate splicing generate additional forms of human HGF R which either lack of the kinase domain, consist of secreted extracellular domains, or are deficient in proteolytic separation of the alpha and beta chains (5-7). The sema domain, which is formed by both the alpha and beta chains of HGF R, mediates both ligand binding and receptor dimerization (3, 8). Ligand-induced tyrosine phosphorylation in the cytoplasmic region activates the kinase domain and provides docking sites for multiple SH2-containing molecules (9, 10). HGF stimulation induces HGF R downregulation via internalization and proteasome-dependent degradation (11). In the absence of ligand, HGF R forms non-covalent complexes with a variety of membrane proteins including CD44v6, CD151, EGF R, Fas, Integrin alpha 6/ beta 4, Plexins B1, 2, 3, and MSP R/Ron (12-19). Ligation of one complex component triggers activation of the other, followed by cooperative signaling effects (12-19). Formation of some of these heteromeric complexes is a requirement for epithelial cell morphogenesis and tumor cell invasion (12, 16, 17). Paracrine induction of epithelial cell scattering and branching tubulogenesis results from the stimulation of HGF R on undifferentiated epithelium by HGF released from neighboring mesenchymal cells (20). Genetic polymorphisms, chromosomal translocation, over-expression, and additional splicing and proteolytic cleavage of HGF R have been described in a wide range of cancers (1). Within the ECD, human HGF R shares 86-88% amino acid sequence identity with canine, mouse, and rat HGF R.

1. Birchmeier, C. et al. (2003) Nat. Rev. Mol. Cell Biol. 4:915.
2. Corso, S. et al. (2005) Trends Mol. Med. 11:284.
3. Gherardi, E. et al. (2003) Proc. Natl. Acad. Sci. USA 100:12039.
4. Park, M. et al. (1987) Proc. Natl. Acad. Sci. USA 84:6379.
5. Crepaldi, T. et al. (1994) J. Biol. Chem. 269:1750.
6. Prat, M. et al. (1991) Mol. Cell. Biol. 12:5954.
7. Rodrigues, G.A. et al. (1991) Mol. Cell. Biol. 11:2962.
8. Kong-Beltran, M. et al. (2004) Cancer Cell 6:75.
9. Naldini, L. et al. (1991) Mol. Cell. Biol. 11:1793.
10. Ponzetto, C. et al. (1994) Cell 77:261.
11. Jeffers, M. et al. (1997) Mol. Cell. Biol. 17:799.
12. Orian-Rousseau, V. et al. (2002) Genes Dev. 16:3074.
13. Klosek, S.K. et al. (2005) Biochem. Biophys. Res. Commun. 336:408.
14. Jo, M. et al. (2000) J. Biol. Chem. 275:8806.
15. Wang, X. et al. (2002) Mol. Cell 9:411.
16. Trusolino, L. et al. (2001) Cell 107:643.
17. Giordano, S. et al. (2002) Nat. Cell Biol. 4:720.
18. Conrotto, P. et al. (2004) Oncogene 23:5131.
19. Follenzi, A. et al. (2000) Oncogene 19:3041.
20. Sonnenberg, E. et al. (1993) J. Cell Biol. 123:223.