Pericellular Activation of Peptide Growth Factors by Serine Proteases

  • Hiroaki Kataoka
  • Tsuyoshi Fukushima
Part of the Current Human Cell Research and Applications book series (CHCRA)


The growth, survival, and metabolic activities of multicellular organisms at the cellular level are regulated not only by intracellular signal transduction pathways but also by systemic homeostasis and the pericellular microenvironment. The significance of the pericellular microenvironment is also established in tumorigenesis and malignant progression of transformed cells, in which processing of bioactive molecules by extracellular proteases has significant roles. Proteolytic activation of peptide growth factors in the pericellular microenvironment enables the induction of outside-in signaling in constituent cells in both physiological and pathological settings. This chapter will review the current knowledge of pericellular activation of peptide growth factors by serine proteases, with the main focus on activation of hepatocyte growth factor (HGF) that transduces signals through the MET receptor tyrosine kinase. There are two mechanisms for HGF activation in vivo: serum activation and cellular activation. Type II transmembrane serine proteases are membrane-anchored proteases that are part of cellular HGF-activating machinery. In the past decade, evidence for the roles of these proteases in cancer progression has been rapidly emerging.


Protease HGF TTSP Matriptase Hepsin HAI-1 HAI-2 


Conflict of Interest

The authors declare no financial and commercial conflicts of interest.


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© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of MedicineUniversity of MiyazakiMiyazakiJapan

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