Mode of receptor binding and activation by plasminogen‐related growth factors

FEBS Letters

Miller, Maria²  Leonard, Edward J¹ 

[1] Laboratory of Immunobiology, NCI-Frederick Cancer Research and Development Center, Frederick, MD 21702, USA;Macromolecular Structure Laboratory, NCI-Frederick Cancer Research and Development Center, ABL-Basic Research Program, Frederick, MD 21702-1201, USA

关键词: Hepatocyte growth factor;    Macrophage stimulating protein;    Plasminogen-related growth factor;    Tumorigenesis;    Receptor oligomerization;   

DOI  :  10.1016/S0014-5793(98)00533-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 αβ chains. Surprisingly, despite structural similarities, the high affinity receptor binding regions of the two proteins are different: α chain for HGF, and β chain for MSP. We propose that after cleavage exposes a β chain binding site (high affinity for MSP, low affinity for HGF), monomeric ligand induces receptor dimerization and activation via α and β chain binding sites of different affinity.

【 授权许可】

Unknown