The glycoprotein Ib IX complex regulates cell proliferation

The glycoprotein (Gp) Ib/IX complex contains three transmembranous leucine-rich repeat polypeptides (GpIb alpha, GpIb beta, and GpIX) that form the platelet von Willebrand factor (VWF) receptor, GpIb/IX functions to effect platelet adhesion, activation, and aggregation under conditions of high shear stress. GpIb/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 GpIb/IX regulates cell growth was investigated. The surface expression of recombinant GpIb alpha decreases the proliferation of transduced CHO cells. GpIb alpha 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 GpIb alpha in heterologous cells requires signaling through the 14-3-3 zeta binding domain of GpIb alpha and is partially dependent on its engagement by the extracellular ligand VWF, Growth arrest induced by the expression of recombinant GpIb/IX is followed by apoptosis of the transduced cells. The endogenous expression of GpIb alpha in human hematopoietic cells is associated with decreased proliferation. These results suggest that the expression of the GpIb/IX complex regulates megakaryocyte growth. (C) 1999 by The American Society of Hematology.