The glycoprotein Ib/IX complex regulates cell proliferation

The glycoprotein (Gp) lb/IX complex contains three transmembranous leucine-rich repeat polypeptides (Gplbα, Gplbβ, and GpIX) that form the platelet von Willebrand factor (vWF) receptor. Gplb/IX functions to effect platelet adhesion, activation, and aggregation under conditions of high shear stress. Gplb/IX is expressed late in the ontogeny of megakaryocytes, the precursor cell that releases platelets when it reaches its terminal stage of differentiation. Because signal pathways can be reused at different stages of development by integration with different effector pathways and because cellular adhesion through other receptor families often modulates cell growth, the hypothesis that Gplb/IX regulates cell growth was investigated. The surface expression of recombinant Gplbα decreases the proliferation of transduced CHO cells. Gplbα causes growth arrest in the G1 phase of the cell cycle associated with the induction of the cyclin-dependent kinase inhibitor p21. G1 arrest induced by recombinant Gplbα in heterologous cells requires signaling through the 14-3-3ζ binding domain of Gplbα and is partially dependent on its engagement by the extracellular ligand vWF. Growth arrest induced by the expression of recombinant Gplb/IX is followed by apoptosis of the transduced cells. The endogenous expression of Gplbα in human hematopoietic cells is associated with decreased proliferation. These results suggest that the expression of the Gplb/IX complex regulates megakaryocyte growth.