PROK1

PROK1 Full Name

prokineticin 1

PROK1 Introduction

Prokineticin 1 (PROK1), also known as Endocrine Gland-Derived Vascular Endothelial Growth Factor (EG-VEGF), is a small, secreted protein and a founding member of the prokineticin family. It is characterized by a conserved five-disulfide bond structure known as the AVIT motif, which is essential for its biological activity. PROK1 signals through two specific G protein-coupled receptors, PROKR1 and PROKR2. It was initially identified as a mitogen specific for vascular endothelial cells within steroidogenic glands (like the adrenal cortex and ovary), distinguishing it from the broader-acting VEGF.

Figure 1. Proposed mechanism of prokineticin 1 (PROK1) for regulating the porcine corpus luteum function.(Source: Baryla, M,2023)

Pathological Significance and Disease Links
Dysregulation of PROK1 signaling is implicated in several pathological conditions. In reproduction, aberrant PROK1 expression is associated with recurrent implantation failure and pregnancy disorders like preeclampsia. Due to its potent angiogenic properties, elevated PROK1 levels have been linked to the progression of various cancers, including those of the ovary, breast, and prostate, where it promotes tumor growth, angiogenesis, and metastasis. Additionally, mutations in the genes for PROK1 or its receptor PROKR2 are a known genetic cause of Kallmann syndrome, characterized by delayed puberty and anosmia (loss of smell).

Expression Regulation and Signaling
The expression of the PROK1 gene is tightly regulated by hormonal signals, particularly by progesterone and hypoxia-inducible factors (HIFs). This regulation links its activity to the menstrual cycle, pregnancy, and low-oxygen environments like solid tumors. Upon binding to its receptors (PROKR1/2), it activates multiple downstream signaling pathways, including PKC, MAPK, and PI3K/Akt. These pathways drive cellular responses such as proliferation, migration, and enhanced survival, mediating its effects in both normal physiology and disease.

Alternate Names for PROK1

PROK1; prokineticin 1; PK1; PRK1; EGVEGF; prokineticin-1; EG-VEGF; mambakine; black mamba toxin-related protein; endocrine-gland-derived vascular endothelial growth factor;

• 1.Baryla, M., Goryszewska-Szczurek, E., Kaczynski, P., Balboni, G., & Waclawik, A. Prokineticin 1 is a novel factor regulating porcine corpus luteum function. Scientific reports, 2023. 13(1), 5085.