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Cloning and developmental expression analysis of the murine c-mer tyrosine kinase
D K Graham1, G W Bowman, T L Dawson
1UNC Lineberger Comprehensive Cancer, University of North Carolina at Chapel Hill 27599-7295, USA.
Abstract:
We have cloned the putative mouse homologue of the human c-mer receptor tyrosine kinase proto-oncogene. Comparison of the mouse and human c-mer amino acid sequences reveals an overall identity of 88%. Similar to the human, the extracellular region of the murine c-mer protein possesses two amino terminal immunoglobulin-like domains and two membrane proximal fibronectin type III domains, which places it in the Axl family of tyrosine kinases. Our analysis of the Axl family identifies eight different regions of amino acid consensus that have residues characteristic of this and no other tyrosine kinase family; six of the eight are within tyrosine kinase subdomains. The homology within the Axl family is highest between c-mer and c-eyk, the chicken proto-oncogene of the tumor virus gene product v-eyk. Northern analysis of adult tissues suggests that the mouse c-mer, although expressed in many tissues, has an expression pattern unique among Axl family members. In normal adult hematopoietic cells c-mer seems to be expressed predominantly if not exclusively in the monocytic lineage. Mouse c-mer is expressed during most, if not all, stages of embryological development beginning in the morula and blastocyst and progressing through the yolk sac and fetal liver stages. This early and consistent expression of c-mer was confirmed during in vitro differentiation of embryonic stem cells. The embryonic expression profile of c-mer suggests that this tyrosine kinase may play an important function in the developing mouse.
Insights
Researchers cloned the mouse c-mer receptor tyrosine kinase, finding 88% amino acid identity with the human homologue. Mouse c-mer is predominantly expressed in monocytic cells and throughout embryonic development, suggesting a key role in development.
Area of Science:
- Molecular Biology
- Genetics
- Developmental Biology
Background:
- The c-mer receptor tyrosine kinase proto-oncogene plays a role in cellular processes.
- Understanding the murine homologue provides insights into conserved and divergent functions.
Purpose of the Study:
- To clone and characterize the mouse homologue of the human c-mer receptor tyrosine kinase.
- To investigate the expression pattern of mouse c-mer in adult tissues and during embryonic development.
Main Methods:
- Cloning of the mouse c-mer gene.
- Amino acid sequence comparison between mouse and human c-mer.
- Northern blot analysis of adult tissues.
- Analysis of c-mer expression during embryonic stem cell differentiation and in embryonic tissues.
Main Results:
- The mouse c-mer shares 88% amino acid identity with the human homologue and possesses characteristic domains of the Axl family of tyrosine kinases.
- Mouse c-mer exhibits a unique expression pattern among Axl family members, predominantly in the monocytic lineage in adult hematopoietic cells.
- Expression is detected throughout most stages of mouse embryological development, from the morula/blastocyst stage through yolk sac and fetal liver development.
- In vitro differentiation of embryonic stem cells confirmed early and consistent c-mer expression.
Conclusions:
- Mouse c-mer is a conserved tyrosine kinase with structural similarities to its human counterpart.
- Its distinct expression patterns in adult hematopoietic cells and early embryonic development suggest critical roles in hematopoiesis and embryogenesis.
- The early and widespread embryonic expression indicates a potentially vital function in mouse development.