Blood, Vol. 96 No. 3 (August 1), 2000:
pp. 794-799
PLENARY PAPER
Molecular characterization of a granulocyte
macrophage-colony-stimulating factor receptor 
subunit-associated
protein, GRAP
Jiangling Tu,
Nicos Karasavvas,
Mark L. Heaney,
Juan Carlos Vera, and
David W. Golde
From the Program in Molecular Pharmacology and Therapeutics
and the Department of Medicine, Memorial Sloane-Kettering Cancer
Center, New York, NY.
The granulocyte macrophage-colony-stimulating factor
receptor (GM-CSF-R) is a heterodimer composed of 2 subunits, 
and
, and ligand binding to the high-affinity receptor leads to
signalling for the multiple actions of GM-CSF on target cells. In order
to explore the role of the subunit in signalling, we used a
yeast-2-hybrid system to identify proteins interacting with the
intracellular domain of the GMR-. A cDNA encoding a predicted
protein of 198 amino acids, designated GRAP (GM-CSF
receptor subunit-associated protein), was isolated in experiments using the
intracellular portion of GMR- as bait. The interaction between GRAP
and GMR- was confirmed by coimmunoprecipitation in mammalian cells.
GRAP mRNA is widely expressed in normal human and mouse tissues and in
neoplastic human cell lines, but it is not restricted to cells or
tissues that express GM-CSF receptors. Three discrete GRAP mRNA species
were detected in human tissues and cells, with estimated sizes of 3.3, 3.1, and 1.3 kb. GRAP is highly conserved throughout evolution, and
homologues are found in yeast. The GRAP locus in Saccharomyces
cerevisiae was disrupted, and mutant yeast cells showed an
inappropriate stress response under normal culture conditions, manifested by early accumulation of glycogen during the logarithmic growth phase. GRAP is, therefore, a highly conserved and widely expressed protein that binds to the intracellular domain of GMR-, and it appears to play an important role in cellular metabolism.
