Distinct structural characteristics of discoidin I subfamily receptor tyrosine kinases and complementary expression in human cancer

Frauke Alves, Wolfgang Vogel, Kevin Mossie, Birgit Millauer, Heinz Höfler, Axel Ullrich

Research output: Contribution to journalArticlepeer-review

227 Scopus citations

Abstract

Mammary carcinoma kinase 10 (MCK-10) and colon carcinoma kinase 2 (CCK-2) constitute a subclass of receptor tyrosine kinases characterized by a discoidin I motif in the extracellular domain and a large cytoplasmic juxtamembrane (JM) region. While the ectodomain structure suggests a common role in cell aggregation, the JM domains of MCK-10 and CCK-2 are structurally most divergent and display features that suggest an involvement in signal generation and definition. MCK-10 occurs in at least three isoforms, which contain alternatively spliced consensus sequences for internalization and SH3 domain interaction. The presence of the 37 amino acid insert affects receptor autophosphorylation and changes ectodomain glycosylation. Proteolytic cleavage within the extracellular domain of MCK-10 generates a membrane-anchored kinase domain and releases a soluble ectodomain fragment including the discoidin I homology domain. CCK-2 and MCK-10 expression was found in connective and epithelial tissues, respectively, which in cancers of epithelial origin results in mutually exclusive expression in stroma and tumor cells, indicating a possible involvement of this class of RTKs in tumor invasion.

Original languageEnglish
Pages (from-to)609-618
Number of pages10
JournalOncogene
Volume10
Issue number3
StatePublished - 2 Feb 1995
Externally publishedYes

Keywords

  • Discoidin I motif
  • Receptor tyrosine kinase
  • SH3 binding site
  • Signal transduction
  • Tumor invasion

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