Disease relevance of Pdlim5

• FHL2 is a LIM-domain protein expressed in myoblasts but down-regulated in malignant rhabdomyosarcoma cells, suggesting an important role of FHL2 in muscle development [1].
• The LIM-finger protein Lmo2, which is activated in T cell leukemias by chromosomal translocations, is required for yolk sac erythropoiesis [2].
• LMO4, a member of the LIM-only family of zinc-finger proteins, is overexpressed in a significant proportion of breast carcinomas and acts as a negative regulator of mammary epithelial differentiation [3].
• The blockage is not overcome by deleting a large portion of the enhancer region (in U3) in recombinant retroviruses (M-MuLVneo delta Enh) [4].

High impact information on Pdlim5

• LIM factor Lhx3 contributes to the specification of motor neuron and interneuron identity through cell-type-specific protein-protein interactions [5].
• Using in vivo function and protein interaction assays, we found that Lhx3 binds directly to the LIM cofactor NLI to trigger V2 interneuron differentiation [5].
• LIM homeodomain codes regulate the development of many cell types, though it is poorly understood how these factors control gene expression in a cell-specific manner [5].
• LIM domains are required for both inhibitory effects on LIM homeodomain transcription factors and synergistic transcriptional activation events [6].
• Neurons induced in explants derived from both diencephalic and telencephalic levels of the neural plate express the LIM homeodomain protein Isl-1, and these neurons possess distinct identities that match those of the ventral neurons generated in these two subdivisions of the forebrain in vivo [7].

Biological context of Pdlim5

• Point mutation of either the PDZ or LIM domain was sufficient to reverse suppression of colony formation, but mutation of the PDZ domain alone was sufficient to abolish enhanced adhesion [8].
• The phenotype could be rescued by a cypher form, which contains the PDZ domain and the ZM motif, but lacks all three LIM domains [9].
• Motor neuron subtypes express unique combinations of LIM-type homeodomain factors that may act as intrinsic genetic regulators of the cytoskeletal events that mediate cell migration, axon navigation or both [10].
• The LIM homeodomain (LIM-HD) proteins, which contain two tandem LIM domains followed by a homeodomain, are critical transcriptional regulators of embryonic development [11].
• The LIM homeodomain protein ISL1 is expressed in all classes of islet cells in the adult and its expression in the embryo is initiated soon after the islet cells have left the cell cycle [12].

Anatomical context of Pdlim5

• We identified Enigma, a PDZ and LIM domain-containing protein that was previously shown to be associated with the actin cytoskeleton [13].
• Enigma localizes to actin filaments in fibroblasts via its PDZ domain, and actin-associated LIM protein binds to and colocalizes with the actin-binding protein alpha-actinin-2 at Z lines in skeletal muscle [14].
• Thus, LIM homeodomain proteins act within motor neurons and cells that guide motor axons to establish the fidelity of a binary choice in axonal trajectory [15].
• Towards cracking the code: LIM protein complexes in the spinal cord [16].
• A major determinant in the cascades is an LIM homeodomain-containing gene, Lmx1b, which is required for the development of all 5-HT neurons in the central nervous system [17].

Associations of Pdlim5 with chemical compounds

• Cypher is a member of a recently emerging family of proteins containing a PDZ domain at their NH(2) terminus and one or three LIM domains at their COOH terminus [18].
• Specificity of LIM domain interactions with receptor tyrosine kinases [19].
• LIM domains, Cys-rich motifs containing approximately 50 amino acids found in a variety of proteins, are proposed to direct protein*protein interactions [19].
• To identify structural targets recognized by LIM domains, we have utilized random peptide library selection, the yeast two-hybrid system, and glutathione S-transferase fusions [19].
• PINCH is a five LIM domain protein involved in the regulation of integrin-mediated cell adhesion [20].

Other interactions of Pdlim5

• This interaction required the NPTY motif of APS and the LIM domains of Enigma [13].
• Mitogenic signaling by Ret/ptc2 requires association with enigma via a LIM domain [21].
• Together, our data suggest that Cypher1 may function as an adaptor in striated muscle to couple protein kinase C-mediated signaling, via its LIM domains, to the cytoskeleton (alpha-actinin-2) through its PDZ domain [22].

Analytical, diagnostic and therapeutic context of Pdlim5

• Reciprocal substitution of the Enh2 domains in the two LTRs by site-directed mutagenesis shows that the rc-mos variant confers a 3-fold increment in in vivo promotor activity [23].
• Molecular cloning, structure, and chromosomal localization of the mouse LIM/homeobox gene Lhx5 [24].
• We report the cloning, sequence analysis, and developmental expression pattern of lim1, a member of the LIM class homeobox gene family in the mouse. lim1 cDNA encodes a predicted 406 amino acid protein that is 93% identical with the product of the Xenopus LIM class homeobox gene Xlim1 [25].
• Reverse transcriptase-polymerase chain reactions (RT-PCR) performed on mouse pituitary mRNA using degenerate oligonucleotides based on the conserved LIM-domain sequences, allowed the extension of the 5' end of the sequence [26].
• NMR titration experiments and site-directed mutagenesis indicate that this result is not dependent on specific interactions that require surface exposed residues on the RIL LIM domain, suggesting a stabilizing role in the association with PTP-BL [27].

References