Abstract
The Met tyrosine kinase receptor has been implicated in human cancer. Here we have examined the signaling requirements of three oncogenic forms of this molecule: wild type Met in response to ligand/autocrine stimulation, Met which has been mutationally activated, and Tpr-Met (a constitutively active truncated Met fusion protein). Previous studies have demonstrated the importance of a Grb2 binding site, and of specific tyrosine residues (i.e. Y8,9 and Y14,15) for Met function, and we have now explored the relevance of these and other sites for oncogenic Met signaling. Following substitution of various intracellular tyrosines for phenylalanine, we find that the transforming activity of each Met oncogene is dependent upon tyrosines Y8,9 and Y14,15, in addition to two novel tyrosines (Y6 and Y10) not previously implicated in Met signaling. Tyrosines Y6 and Y10 influence a variety of Met-mediated responses both in vitro (transformation, mitogenicity and invasion), and in vivo (tumorigenicity and metastasis). We also show that Tpr-Met is much more dependent on its Grb2 binding site for biological activity than are the other oncogenic forms of the Met receptor. Thus, although the three Met oncogenes examined are similar in their dependency on a number of specific tyrosines for activity, the signaling strategy employed by Tpr-Met can be differentiated from that of the other two.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Additional information
By acceptance of this article, the publisher or recipient acknowledges the right of the U.S. Government and its agents and contractors to retain a nonexclusive royalty-free license in and to any copyright covering the article.
Rights and permissions
About this article
Cite this article
Jeffers, M., Koochekpour, S., Fiscella, M. et al. Signaling requirements for oncogenic forms of the Met tyrosine kinase receptor. Oncogene 17, 2691–2700 (1998). https://doi.org/10.1038/sj.onc.1202209
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1202209
Keywords
This article is cited by
-
Comment on “Effect of transferred NK4 gene on proliferation, migration, invasion, and apoptosis of human prostate cancer DU145 cells” by Dan Yue et al. in Asian Journal of Andrology
Asian Journal of Andrology (2010)
-
Progesterone receptor A and c-Met mediates spheroids-endometrium attachment
Reproductive Biology and Endocrinology (2009)
-
Oncogenic Met receptor induces ectopic structures in Xenopus embryos
Oncogene (2006)
-
Use of signal specific receptor tyrosine kinase oncoproteins reveals that pathways downstream from Grb2 or Shc are sufficient for cell transformation and metastasis
Oncogene (2002)
-
Cross-talk between the proto-oncogenes Met and Ron
Oncogene (2000)