The kinase-inactive PDGF β-receptor mediates activation of the MAP kinase cascade via the endogenous PDGF α-receptor in HepG2 cells

The PDGF β-receptor in which the active-site lysine in the kinase domain has been mutated to arginine (K634R) lacks intrinsic kinase activity. When expressed in HepG2 cells, the kinase-inactive PDGF β-receptor was tyrosine phosphorylated in response to PDGF-BB. Previously, HepG2 cells were thought to be devoid of PDGF α-receptor primarily due to lack of specific antibody which precluded detection of the PDGF α-receptor. In fact, these cells express low levels of PDGF α-receptor. In HepG2 cells that express the kinase-inactive PDGF β-receptor, PDGF-BB activates the PDGF α-receptors to trans phosphorylate the kinase-inactive PDGF β-receptor in an intermolecular fashion. As a result, stimulation of HepG2 cells that express the kinase-inactive receptor leads to activation of serine/threonine kinases of the MAP kinase cascade which include RAF-1, MEK-1 and p42 MAP kinase. In contrast, the kinase-inactive receptor does not activate any signaling pathways when it is expressed in PC12 cells which do not express the endogenous PDGF α-receptor. Thus, the kinase-inactive K634R PDGF β-receptor is able to enhance PDGF-BB signaling in HepG2 cells that express the PDGF α-receptor.