Phosphorylation and Protein-Protein Interactions in Signal Transduction 
Receptor Tyrosine Kinases 
in Embryonic Development 
We have recently cloned cDNAs for two novel 
receptor tyrosine kinases, elk and nuk, which are 
primarily expressed in the mammalian nervous 
system. During formation of the nervous system 
in the early mouse embryo, nuk assumes a very 
specific and interesting pattern of expression. We 
are using genetic manipulation in the mouse to 
determine whether nuk is involved in control- 
ling neural differentiation. 
Dual-Specificity Protein Kinases 
Protein kinases are typically divided into those 
that can phosphorylate serine/threonine residues 
and those that phosphorylate tyrosine. We have 
recently identified two mammalian protein ki- 
nases that can phosphorylate both serine/threo- 
nine and tyrosine when artificially expressed in 
bacteria. We are investigating the significance of 
this observation for mammalian cells. 
One of these kinases, Clk, is related to 
members of the cdc2 protein kinase family. The 
second. Nek, is similar to the product of the 
nimA gene, required for initiation of mitosis in 
the fungus Aspergillus nidulans. The identifica- 
tion of nek as a mouse relative of nimA suggests 
that this gene may have been conserved in evolu- 
tion, as have other members of the cell cycle ma- 
chinery. These observations prompt the specula- 
tion that control of the cell cycle involves protein 
kinases with dual specificity. 
Additional funding for this work was provided 
by the National Cancer Institute of Canada and 
the Medical Research Council of Canada. 
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