PTPRF

Case Study 1: Mai Quynh Nguyen, 2022

Actin-based protrusions called cytonemes are reported to function in cell communication by supporting events such as morphogen gradient establishment and pattern formation. Despite the crucial roles of cytonemes in cell signaling, the molecular mechanism for cytoneme establishment remains elusive. In this study, the researchers showed that the leukocyte common antigen-related (LAR) receptor protein tyrosine phosphatase plays an important role in cytoneme-like protrusion formation. Overexpression of LAR in HEK293T cells induced the formation of actin-based protrusions, some of which exceeded 200 μm in length and displayed a complex morphology with branches. Upon focusing on the regulation of LAR dimerization or clustering and the resulting regulatory effects on LAR phosphatase activity, they found that longer and more branched protrusions were formed when LAR dimerization was artificially induced and when heparan sulfate was applied. Interestingly, although the truncated form of LAR lacking phosphatase-related domains promoted protrusion formation, the phosphatase-inactive forms did not show clear changes, suggesting that LAR dimerization triggers the formation of cytoneme-like protrusions in a phosphatase-independent manner.

Fig1. Analytical results of the changes in detected luminescence upon rapamycin application to induce LAR dimerization followed by reconstitution and restoration of luciferase enzymatic activity (at 60 min post application).

Fig2. Representative images from three independent trials showing the effects of heparan sulfate (HS) and chondroitin sulfate (CS) treatments on LAR- or mutated LAR*- induced protrusion formation.

Case Study 2: J M Zabolotny, 2001

Previous reports indicate that the expression and/or activity of the protein-tyrosine phosphatase (PTP) LAR are increased in insulin-responsive tissues of obese, insulin-resistant humans and rodents, but it is not known whether these alterations contribute to the pathogenesis of insulin resistance. To address this question, the researchers generated transgenic mice that overexpress human LAR, specifically in muscle, to levels comparable to those reported in insulin-resistant humans. In LAR-transgenic mice, fasting plasma insulin was increased 2.5-fold compared with wild-type controls, whereas fasting glucose was normal. Whole-body glucose disposal and glucose uptake into muscle in vivo were reduced by 39-50%. Insulin injection resulted in normal tyrosyl phosphorylation of the insulin receptor and insulin receptor substrate 1 (IRS-1) in muscle of transgenic mice. However, phosphorylation of IRS-2 was reduced by 62%, PI3' kinase activity associated with phosphotyrosine, IRS-1, or IRS-2 was reduced by 34-57%, and association of p85alpha with both IRS proteins was reduced by 39-52%. Thus, overexpression of LAR in muscle causes whole-body insulin resistance, most likely due to dephosphorylation of specific regulatory phosphotyrosines on IRS proteins.

Fig3. Reactivity of anti-human LAR antibody to human and mouse LAR.

Fig4. Ex vivo insulin signaling in muscle of MCK-hLAR mice. Phosphorylation of IR and IRS-1.

Fig1. Schematic model of miR-145-5p-mediated activation of STAT1 signaling. (Benjamin Goeppert, 2019)

Fig2. Schematic representation of the insulin-signaling pathway. (Carlo de Lorenzo, 2013)

PTPRF involved in several pathways and played different roles in them. We selected most pathways PTPRF participated on our site, such as Cell adhesion molecules (CAMs), Adherens junction, Insulin signaling pathway, which may be useful for your reference. Also, other proteins which involved in the same pathway with PTPRF were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

PTPRF has several biochemical functions, for example, chondroitin sulfate proteoglycan binding, heparin binding, protein complex binding. Some of the functions are cooperated with other proteins, some of the functions could acted by PTPRF itself. We selected most functions PTPRF had, and list some proteins which have the same functions with PTPRF. You can find most of the proteins on our site.

PTPRF has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with PTPRF here. Most of them are supplied by our site. Hope this information will be useful for your research of PTPRF.

CAV1; Irs1; PRPF40A; SKIL; ZNF512B; EGFR