Identification of a Competitive HGF Antagonist Encoded by an Alternative Transcript

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Abstract
We identified a naturally occurring hepatocyte growth factor (HGF) variant, whose predicted sequence extends only through the second kringle domain of this plasminogen-related molecule. This smaller molecule, derived from an alternative HGF transcript, lacked mitogenic activity but specifically inhibited HGF-induced mitogenesis. Cross-linking studies demonstrated that the truncated molecule competes with HGF for binding to the HGF receptor, which has been identified as the c- met protooncogene product. Thus, the same gene encodes both a growth factor and its direct antagonist.