Mode of receptor binding and activation by plasminogen-related growth factors.
Hepatocyte growth factor/scatter factor (HGF/SF) and macrophage stimulating protein (MSP) are plasminogen-related kringle proteins that lost serine protease domain enzymatic activity and became ligands for cell surface tyrosine kinase receptors. They are activated by cleavage to disulfide-linked alphabeta chains. Surprisingly, despite structural similarities, the high affinity receptor binding regions of the two proteins are different: alpha chain for HGF, and beta chain for MSP. We propose that after cleavage exposes a beta chain binding site (high affinity for MSP, low affinity for HGF), monomeric ligand induces receptor dimerization and activation via alpha and beta chain binding sites of different affinity.
Miller
M
M
Macromolecular Structure Laboratory, NCI-Frederick Cancer Research and Development Center, ABL-Basic Research Program, MD 21702-1201, USA.
Leonard
E J
EJ
D000818:Animals; D001665:Binding Sites; D019281:Dimerization; D017228:Hepatocyte Growth Factor / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D018082:Kringles / Q000502:physiology; D016173:Macrophage Colony-Stimulating Factor / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism
D017228:Hepatocyte Growth Factor; D016173:Macrophage Colony-Stimulating Factor; D019859:Proto-Oncogene Proteins c-met