The Molecular History of Eukaryotic Life  Single Transmembrane Segment Receptors 


David Nelson  Dec. 13, 2000

	Some receptors with single transmembrane segments unite as dimers and have 
enzymes associated with them on the cytosolic side of the membrane.  These enzymes can 
be tyrosine kinases, serine/threonine kinases, tyrosine phosphatases, guanylyl cyclases 
that form cGMP or histidine kinases.  The histidine kinases are ancient signal 
tranduction molecules found in all three domains of life.  These are called two component 
regulators. This system is used in bacterial chemotaxis, where a receptor binding ligand 
activates a histidine kinase CheA to phosphorylate itself.  The PO4 group is rapidly 
transfered to an Asp residue on another soluble protein CheY called the response 
regulator.  This protein then carries out some regulatory function.  In chemotaxis CheY 
binds to the flagellar motor and influences the direction it turns. Clockwise rotation 
causes tumbling which is a kind of retreat from a repellant substance.  Counterclockwise 
rotation makes the E. coli swim smoothly ahead.  CheY that is phosphorylated causes 
clockwise rotation.  The HtrI and HtrII proteins of Halobacterium are similar to CheA,
except they have two transmembrane segments instead of one.  

	Dictyostelium has a his kinase response regulator system.  The receptor DhkA 
binds a secreted peptide SDF2 that triggers autophosphorylation on histidine.  The PO4 is 
transfered to RegA, a cAMP phosphodiesterase which is inhibited.  The increase in cAMP 
activates PKA.  

	Yeast also has one of these response regulatory his kinase receptors for sensing 
osmotic stress.  It feeds into the Hog1 MAP kinase pathway (see below).

	Receptor tyrosine kinases are only found in metazoa[animals] (J. Mol. Evol. 44, 242-252 
1998).  One has been cloned from a sponge, which is as far back as one can go in the 
metazoa.  This gene is interesting because it contains only two introns.  More advanced 
animals have more introns in their tyrosine kinase genes.  Since the sponge gene appears 
to branch on a tree before the other metazoan receptor tyrosine kinases, this suggests 
that introns were added after this branching occurred, favoring the introns late theory.

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