Disease relevance of Linker

• Epidermolysis bullosa simplex (Weber-Cockayne) associated with a novel missense mutation of Asp328 to Val in Linker 12 domain of keratin 5 [1].
• To overcome multi-drug resistance, we engineered a diphtheria fusion protein by fusing human interleukin-3 (IL3) to a truncated form of diphtheria toxin (DT) with a (G4S)2 linker (L), expressed and purified the recombinant protein, and tested the cytotoxicity of the DTLIL3 molecule on human leukemias and normal progenitors [2].
• Targeted prodrug treatment of HER-2-positive breast tumor cells using trastuzumab and paclitaxel linked by A-Z-CINN Linker [3].

High impact information on Linker

• Our results indicate that the PKCtheta-induced phosphorylation of CARMA1 likely occurs on Ser552 on the Linker region of CARMA1 [4].
• 3. Linker-scanning mutations demonstrated that multiple interdependent elements are required for inducibility by PMA and also for synergy with IL-4 [5].
• Receptor and kinase activation is linked to distal signaling pathways (PLC-gamma1 activation, Ca2+ influx, PKC activation and Ras/Erk activation) via the adapter protein LAT (Linker for Activation of T cells) [6].
• The Role of X/Y Linker Region and N-terminal EF-hand Domain in Nuclear Translocation and Ca2+ Oscillation-inducing Activities of Phospholipase C{zeta}, a Mammalian Egg-activating Factor [7].
• The Slp4-a Linker Domain Controls Exocytosis through Interaction with Munc18-1{middle dot}Syntaxin-1a Complex [8].

Biological context of Linker

• Here we have examined how amino acid sequences encompassing the dual phosphorylation motif located in the loop 12 linker (L12) between kinase subdomains VII and VIII and the length and amino acid sequence of L12 influence autophosphorylation, substrate specificity, and upstream kinase selectivity for the MAPK p38 [9].
• Overexpression of the Linker histone-binding protein tNASP affects progression through the cell cycle [10].
• The "Linker" Region (Amino Acids 38-47) of the Disintegrin Elegantin Is a Novel Inhibitory Domain of Integrin {alpha}5beta1-Dependent Cell Adhesion on Fibronectin: EVIDENCE FOR THE NEGATIVE REGULATION OF FIBRONECTIN SYNERGY SITE BIOLOGICAL ACTIVITY [11].
• In this study, green fluorescent protein was fused to full-length CheB or its various parts: the N-terminal regulatory domain (N), the C-terminal catalytic domain (C) and the linker (L) [12].
• The plasmids were made in two configurations, expressing either the VH (pc1A7VHLnVL) or the VL (pc1A7VLLnVH) chain of 1A7 at the amino terminus, linked together by a 15-amino acid linker (Ln) [13].

Anatomical context of Linker

• Red blood cells were labeled using PKH26-GL Red Fluorescent Cell Linker and served as a marker for blood flow and volume [14].

Associations of Linker with other chemical compounds

• Proteolytic Cleavage of the Linker Region of the Human P-glycoprotein Modulates Its ATPase Function [15].
• The enzyme heparinase (Linker & Hovingh 1972) has been used successfully to eliminate heparin inhibition from DNA samples post-extraction, because the normal range of DNA extraction techniques fail to do so (Beutler et al. 1990; Oberhauser et al. 1994; Taylor et al. 1994) [16].
• The adapter molecule LAT (Linker for the Activation of T cells) is a membrane protein that becomes phosphorylated on conserved tyrosine residues upon TCR/CD3 complex engagement in T lymphocytes [17].

Gene context of Linker

• Studies of MRP1 topology suggested the presence of a hydrophobic N-domain with five potential membrane-spanning domains linked to an MDR1-like core (MSD1-NBD1-L1-MSD2-NBD2) by an intracellular linker domain (L0) [18].
• A recombinant PTK6 Kinase domain connected to the Linker region had catalytic activity in terms of autophosphorylation, phosphorylation of a PTK6 substrate, BKS, and phosphorylation of an oligopeptide substrate, whereas the Kinase domain itself, or one connected to a Linker region containing a W184A substitution, did not [19].
• A Smad4 construct, S4AF, consisting of the middle linker (L) domain and the C-terminal (C) domain, is shown to be a monomer, while a Smad3 construct, S3LC, consisting of the LC domains, is shown to form a trimer with an affinity K(3) = (1.2-3.1) x 10(9) M(-2) [20].
• A construct with a 22-amino-acid flexible linker (L22) between the HBEGF and SAP moieties exhibited an affinity for the EGFR that was comparable to that of HBEGF [21].
• Co-expression of the core with the N-terminal region including L0 fully restored MRP1 function [22].

Analytical, diagnostic and therapeutic context of Linker

• Whole genome amplification for CGH analysis: Linker-adapter PCR as the method of choice for difficult and limited samples [23].
• Mass Spectrometric Mapping of Linker Histone H1 Variants Reveals Multiple Acetylations, Methylations, and Phosphorylation as Well as Differences between Cell Culture and Tissue [24].

References