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Understanding Anaplastic Lymphoma Kinase signaling using Drosophila and mouse models


Ruth Palmer

Contact Information | List of Publications | External website

 

Our lab has a strong focus working with Drosophila melanogaster as a genetic model as well as with cultured, tumour-derived human cells. Recently, we have extended our studies to transgenic mice and xenograft models. Therefore, we employ molecular biology, histology and modern microscopy techniques.


Our main interest is in the Drosophila Alk receptor tyrosine kinase, which is expressed in the embryonic visceral mesoderm of the fruit fly, where it has been well characterized. Loss of Alk, or its ligand Jelly Belly (Jeb), results in impaired specification of the visceral muscle founder cells, resulting in a failure of cell fusion, leading to late embryonic/early larval lethality. Activation of Alk by Jeb leads to activation of a signaling pathway in the visceral mesoderm that directs specification of muscle founder cells.


In humans inappropriate activation of Anaplastic Lymphoma Kinase (ALK) in cancer is commonly due to fusion of the ALK kinase domain with a dimerization partner that drives activation. However, ALK activation also occurs in the context of the full length receptor, e.g. as activating point mutations in neuroblastoma. In many additional tumor types ALK overexpression and activation has been described, and it is unclear whether this is dependent on activity of a ligand.


Vertebrate ALK shares kinase domain similarities as well as a glycine-rich region in the membrane proximal portion of their extracellular domains with the related Leukocyte Tyrosine Kinase (LTK) RTK. ALK mRNA expression is found in a number of human tissues including adult brain, small intestine, colon, prostate and testis. The neuronal expression of ALK suggests a function for the ALK this receptor in the developing nervous system. Ligands for human ALK have recently been identified as FAM150A and FAM150B, which bind to the extracellular domain of ALK and potently activate it.


Current projects are investigating ALK signaling components in both Drosophila and vertebrate systems.

Ruth Palmer

Contact Information

List of Publications

External website

Group Members

Yasuo Yamazaki PhD, Post-doc
Georg Wolfstetter PhD, Post-doc
Kathrin Pfeifer PhD, Post-doc
Fredrik Hugosson PhD, Post-doc
Patricia Mendoza PhD student
Piyush Patel PhD student

Sidansvarig: Dan Baeckström|Sidan uppdaterades: 2016-02-22
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