Leupaxin is a novel LIM domain protein that forms a complex with PYK2
B P Lipsky1, C R Beals, D E Staunton
1ICOS Corporation, Bothell, Washington 98021, USA.
Insights
We discovered leupaxin, a novel protein in hematopoietic cells, homologous to paxillin. Leupaxin may regulate PYK2 signaling complexes in leukocytes, functioning as a phosphotyrosine protein.
Area of Science:
- Cell Biology
- Molecular Biology
- Immunology
Background:
- Leupaxin is a novel cytoplasmic protein preferentially expressed in hematopoietic cells.
- It shares homology with paxillin, a focal adhesion protein.
- Leukocytes express leupaxin and PYK2, suggesting a potential cell type-specific signaling complex.
Purpose of the Study:
- To identify and characterize leupaxin, a novel protein in hematopoietic cells.
- To investigate the interaction of leupaxin with focal adhesion kinase (FAK) family members.
- To explore the role of leupaxin in tyrosine kinase signaling pathways in leukocytes.
Main Methods:
- Protein homology analysis comparing leupaxin to paxillin.
- Identification of protein interaction domains (LIM and LD motifs) in leupaxin.
- Co-immunoprecipitation assays to demonstrate leupaxin-PYK2 association.
- Tyrosine kinase assays to assess leupaxin phosphorylation in lymphoid cells.
Main Results:
- Leupaxin possesses LIM domains homologous to paxillin, suggesting focal adhesion localization.
- Leupaxin contains LD motifs similar to those involved in focal adhesion kinase (FAK) binding.
- Leupaxin associates with PYK2, a FAK family member, and is a substrate for tyrosine kinase in lymphoid cells.
- Leupaxin is expressed in FAK-deficient cells like macrophages, indicating alternative signaling pathways.
Conclusions:
- Leupaxin is a novel phosphotyrosine protein with paxillin-like domains, preferentially expressed in hematopoietic cells.
- Leupaxin may assemble and regulate PYK2 signaling complexes in leukocytes.
- Leupaxin's function is likely linked to tyrosine kinase activity in immune cells.
Abstract:
We have identified a novel cytoplasmic protein, leupaxin, that is preferentially expressed in hematopoietic cells and is most homologous to the focal adhesion protein, paxillin. Leupaxin possesses two types of protein interaction domains. There are four carboxyl-terminal LIM domains in leupaxin that share 70% amino acid identity and 80% similarity with those in paxillin. Paxillin LIM domains mediate localization to focal contacts. In the amino-terminal region of leupaxin there are three short stretches of approximately 13 amino acids that share 70-90% similarity with paxillin LD motifs. Paxillin LD motifs have been implicated in focal adhesion kinase (FAK) and vinculin binding resulting in the localization of FAK to focal adhesions. Leupaxin is expressed in cell types, such as macrophage, that lack FAK. We demonstrate here that leupaxin associates with a second FAK family member, PYK2. As leupaxin and PYK2 are both preferentially expressed in leukocytes they may therefore form a cell type-specific signaling complex. We also demonstrate that leupaxin is a substrate for a tyrosine kinase in lymphoid cells and thus may function in and be regulated by tyrosine kinase activity. Leupaxin is thus a phosphotyrosine protein with LD and LIM binding motifs most homologous to paxillin that may assemble and regulate PYK2 signaling complexes in leukocytes.
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