PTPRK, or Protein Tyrosine Phosphatase Receptor Type K, is a protein belonging to the protein tyrosine phosphatase (PTP) family of enzymes. As a receptor PTP, it is located on the cell surface, receiving signals from the external environment. Through its enzymatic activity, PTPRK regulates various cellular processes, including cell signaling, which is how cells communicate and coordinate activities.
How PTPRK Works
PTPRK functions as an enzyme, removing phosphate groups from specific tyrosine residues on other proteins through a process called dephosphorylation. This action opposes protein tyrosine kinases, which add phosphate groups. The balance between phosphorylation and dephosphorylation is tightly controlled and fundamental for proper cell signaling.
PTPRK’s dephosphorylation activity regulates cellular processes like cell growth, differentiation, and the cell cycle. By removing phosphate groups, PTPRK can switch proteins “off” or change their activity, influencing how cells respond to internal and external cues. For example, PTPRK directly dephosphorylates proteins involved in cell adhesion, such as Afadin, PARD3, and delta-catenin family members, which is important for maintaining cell junction integrity.
Research suggests PTPRK’s tumor-suppressing ability may involve mechanisms beyond its direct phosphatase activity. It can influence gene expression related to epithelial cell identity and tissue repair, indicating additional roles as an adaptor or scaffold protein.
PTPRK’s Role in Cellular Processes
PTPRK is involved in normal biological processes, particularly cell-cell interactions and tissue organization. It plays a role in cell adhesion, where cells stick to each other and their environment. This function is supported by its ability to accumulate at cell-cell contacts and stabilize at the plasma membrane through interactions with other PTPRK molecules.
The protein also impacts cell migration, the directed movement of cells. In colorectal cancer cells, PTPRK promotes collective, directed migration and suppresses invasion. This indicates its involvement in maintaining organized cell movement, important for tissue development and repair.
PTPRK contributes to the integrity of cell-cell junctions. The loss of PTPRK’s phosphatase activity can disrupt these junctions, leading to increased invasive characteristics. This highlights its significance in maintaining healthy tissue structure and function.
PTPRK and Health Conditions
PTPRK is widely recognized as a tumor suppressor gene; its dysfunction or altered expression can contribute to cancer development. The gene encoding PTPRK is located on chromosome 6q, a region frequently deleted in various cancers. Loss or mutation of PTPRK can lead to increased cell proliferation, adhesion, and migration, behaviors associated with cancer progression.
In colorectal cancer, PTPRK has been shown to suppress tumor growth in mouse models and human colorectal cancer cells. It regulates growth factor and adhesion signaling and helps suppress epithelial to mesenchymal transition (EMT), a process where cells lose their adhesion properties and become more migratory, which is often linked to cancer metastasis. PTPRK also negatively regulates the Wnt signaling pathway, which is often overactive in many cancers.
Beyond colorectal cancer, PTPRK’s reduced expression is linked to shorter survival times and increased metastasis in breast cancer patients. It is also implicated in other malignancies, including glioblastoma, where loss-of-function mutations have been identified. PTPRK has also been found to directly dephosphorylate STAT3, an oncoprotein often activated in various cancers, including nasal NK/T-cell lymphoma.
PTPRK has also been associated with other health conditions beyond cancer. Single nucleotide polymorphisms (SNPs) within the PTPRK gene have been linked to an increased risk of Alzheimer’s disease and can influence the age at which the disease begins. These genetic variations are also associated with cholesterol levels, specifically LDL and total cholesterol. PTPRK polymorphisms have been connected to psychiatric disorders such as schizophrenia, major depressive disorder, and bipolar disorder.