MERTK

Case study 1: Seba Almedawar, 2020

Maintenance of a healthy photoreceptor-retinal pigment epithelium (RPE) interface is essential for vision. At the center of this interface, apical membrane protrusions stemming from the RPE ensheath photoreceptor outer segments (POS), and are possibly involved in the recycling of POS through phagocytosis. The molecules that regulate POS ensheathment and its relationship to phagocytosis remain to be deciphered.

By means of ultrastructural analysis, the researchers revealed that MERTK ligands, GAS6 and PROS1, rather than αVβ5 integrin receptor ligands, triggered POS ensheathment by human embryonic stem cell (hESC)-derived RPE. Consistently, POS ensheathment, fragmentation, and internalization were abolished in MERTK mutant RPE, and rescue of MERTK expression in retinitis pigmentosa (RP38) patient RPE counteracted these defects. The results suggest that loss of ensheathment due to MERTK dysfunction might contribute to vision impairment in RP38 patients.

Fig1. Immunoblot (western blot) analysis of MERTK using total protein extracts from wild-type and MERTK mutant RPE.

Fig2. MERTK Mutations in Human RPE Abolish POS Ensheathment. SEM images of wild-type and MERTK mutant RPE treated with F-POS and 30% serum. (E) Wild-type hESC-RPE. (F) MERTK mutant MERTK-RPE. (G) MERTK mutant EX2-RPE. (H) MERTK mutant EX14-RPE.

Case study 2: Frank C Cackowski, 2017

Many prostate cancer (PCa) recurrences are thought to be due to reactivation of disseminated tumor cells (DTCs). The researchers previously found a role of the TAM family of receptor tyrosine kinases TYRO3, AXL, and MERTK in PCa dormancy regulation. However, the mechanism and contributions of the individual TAM receptors is largely unknown.

Knockdown of MERTK, but not AXL or TYRO3 by shRNA in PCa cells induced a decreased ratio of P-Erk1/2 to P-p38, increased expression of p27, NR2F1, SOX2, and NANOG, induced higher levels of histone H3K9me3 and H3K27me3, and induced a G1/G0 arrest, all of which are associated with dormancy. Also knockdown of MERTK in PCa cells increased metastasis free survival in an intra-cardiac injection mouse xenograft model. MERTK knockdown also failed to inhibit PCa growth in vitro and subcutaneous growth in vivo. Overall, this study shows that MERTK stimulates PCa dormancy escape through a MAP kinase dependent mechanism, also involving p27, pluripotency transcription factors, and histone methylation.

Fig3. Effect of MERTK knockdown on growth of prostate cancer cells in culture and in subcutaneous tumors.

Fig4. Control or shMER PC3 cells cultured with 5 μM SB203580 or 0.05% DMSO solvent control for 14 days in 10% serum and 3 days in 0.1% serum followed by cell cycle analysis with total DNA and BrdU labeling as described.

Fig1. Updated pathogenetic model of IgG4-RD Apoptotic phenomena triggered by CD4+ CTLs activate scavenger MerTK+ macrophages through ProS1 ligation. (Lucrezia Rovati, 2021)

Fig2. MERTK stimulates PCa dormancy escape through a MAP kinase dependent mechanism, also involving p27, pluripotency transcription factors, and histone methylation. (Frank C Cackowski, 2017)

MERTK involved in several pathways and played different roles in them. We selected most pathways MERTK participated on our site, such as Cell surface interactions at the vascular wall, Hemostasis, which may be useful for your reference. Also, other proteins which involved in the same pathway with MERTK were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

MERTK has several biochemical functions, for example, ATP binding, protein binding, transmembrane receptor protein tyrosine kinase activity. Some of the functions are cooperated with other proteins, some of the functions could acted by MERTK itself. We selected most functions MERTK had, and list some proteins which have the same functions with MERTK. You can find most of the proteins on our site.

MERTK 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 MERTK here. Most of them are supplied by our site. Hope this information will be useful for your research of MERTK.

saicar; PKM; abl-tide; HSP90AB1; q5nhh0_fratt; mpl; crizotinib