PAPPA

PAPPA Full Name

pregnancy-associated plasma protein A, pappalysin 1

PAPPA Introduction

PAPP-A exists as pregnancy-associated plasma protein A or pappalysin 1 which functions as a large zinc-binding metalloproteinase that regulates insulin-like growth factor (IGF) signaling pathways. The plasma of pregnant women contains high levels of this protein which also exists in non-pregnant tissues including cardiovascular system and ovary and bone. The protein PAPP-A achieves its function through the cleavage of IGF-binding proteins (IGFBP-4 and IGFBP-5) which results in higher IGF concentrations that promote cell growth and differentiation and survival.

Figure 1. A simplified model for the regulation of PAPP-A activity by proMBP or STC2.(Source: Zhong Q, et al. 2022)

Functionally, PAPP-A acts as a regulator of IGF-dependent cellular processes, influencing tissue growth, remodeling, and repair. The enzyme activates IGF signaling through proteolytic activity which produces effects on angiogenesis and wound healing and placental development. The protein shows dynamic expression patterns during disease states which makes it a promising biomarker and therapeutic target. The enzyme operates under strict control because uncontrolled activity disrupts tissue equilibrium and leads to disease advancement.

Medical research shows that elevated PAPP-A levels appear in different disease conditions. The measurement of PAPP-A levels during early pregnancy helps doctors predict which women will develop preeclampsia and experience fetal growth problems and chromosomal abnormalities. Research shows that PAPP-A blood levels in non-pregnant patients link to unstable plaques which raise their chances of experiencing acute coronary events. Research indicates PAPP-A supports tumor expansion and metastasis in specific cancers through IGF signaling pathways which makes it a valuable diagnostic tool and therapeutic candidate.

Alternate Names for PAPPA

PAPPA; pregnancy-associated plasma protein A, pappalysin 1; PAPA; DIPLA1; PAPP-A; PAPPA1; ASBABP2; IGFBP-4ase; pappalysin-1; IGF-dependent IGFBP-4 protease

• 1.Zhong Q, et al. Structural insights into the covalent regulation of PAPP-A activity by proMBP and STC2. Cell Discov. 2022, 8(1):137.