A receptor tyrosine kinase found in breast carcinoma cells has an extracellular discoidin I-like domain
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J D Johnson1, J C Edman, W J Rutter
1Hormone Research Institute, University of California, San Francisco 94143-0534.
Abstract:
We have identified a breast carcinoma tyrosine phosphoprotein, discoidin domain receptor (DDR), that defines an unusual class of receptor tyrosine kinases. The DDR cDNA predicts a C-terminal tyrosine kinase domain and an N-terminal domain similar to the Dictyostelium discoideum lectin discoidin I. These domains are connected by an extraordinary hydrophilic proline/glycine-rich domain, which is interrupted by a predicted transmembrane sequence. This extended proline/glycine-rich region may be required for an unusual geometry of interaction with ligand or substrates. Discoidin I domains are also found in other proteins, including coagulation factors V and VIII, and may represent a class of domains that interact with specific cell surface molecules.
Insights
Researchers discovered discoidin domain receptor (DDR), a novel breast carcinoma tyrosine phosphoprotein. This protein kinase may interact with cell surface molecules, defining a new class of receptor tyrosine kinases.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Receptor tyrosine kinases (RTKs) are crucial cell signaling proteins.
- Dysregulation of RTKs is implicated in various cancers, including breast carcinoma.
- Novel RTKs may offer new therapeutic targets.
Purpose of the Study:
- To identify and characterize novel receptor tyrosine kinases involved in breast carcinoma.
- To elucidate the structural features and potential function of the newly identified protein.
Main Methods:
- cDNA identification and sequencing.
- Bioinformatic analysis of predicted protein domains.
- Comparative analysis with known protein families.
Main Results:
- Identification of discoidin domain receptor (DDR) as a breast carcinoma tyrosine phosphoprotein.
- DDR possesses a unique structure with a C-terminal tyrosine kinase domain and an N-terminal discoidin I-like domain.
- An extended proline/glycine-rich region and a transmembrane sequence were predicted.
Conclusions:
- DDR represents an unusual class of receptor tyrosine kinases.
- The unique structural features suggest novel ligand or substrate interaction mechanisms.
- Discoidin I domains may mediate interactions with cell surface molecules, potentially impacting cancer progression.