Disease relevance of PCP2

• Expression of PCP-2 in SW480 colon cancer cells can lead to stabilization of cytosolic pools of beta-catenin perhaps, by virtue of their physical interaction [1].
• The L7/L12 gene was expressed in Lactococcus lactis, the model LAB, under the nisin-inducible promoter [2].
• Production and targeting of the Brucella abortus antigen L7/L12 in Lactococcus lactis: a first step towards food-grade live vaccines against brucellosis [2].

High impact information on PCP2

• Protein-tyrosine phosphatase PCP-2 inhibits beta-catenin signaling and increases E-cadherin-dependent cell adhesion [1].
• Human L7 mRNA was cloned from activated T-lymphocytes [3].
• Although no specific function of L7 in the translation apparatus is known as yet, it should be a critical one as indicated by its high degree of structural conservation during evolution and its regulated expression in lymphoid cells [3].
• G-protein alpha subunit interaction and guanine nucleotide dissociation inhibitor activity of the dual GoLoco motif protein PCP-2 (Purkinje cell protein-2) [4].
• Mutational analysis of a non-canonical residue (glycine 24) in human PCP-2 GL1 provided evidence for heterogeneity in mechanisms of Galphai interactions with GoLoco motifs [4].

Biological context of PCP2

• Collectively, the data demonstrate that PCP-2 is a comparatively weak GoLoco motif protein that exhibits highest affinity interactions and GDI activity toward Galphai1, Galphai2, and Galphai3 subunits [4].
• The in vitro stimulation of translation-uncoupled EF-G-dependent GTP-hydrolysis seems to be an intrinsic property of the ribosome that is dependent on L7/L12, reaches a maximum with four copies of the proteins per particle, and reflects the in vivo hydrolysis rate during translation [5].

Anatomical context of PCP2

• The conservation of all of these properties of both the L7/Pcp-2 protein and mRNA highlights their likely importance in controlling the development and/or motor control function of Purkinje cells [6].
• In addition we performed in situ hybridization on a developmental series of human cerebellar sections and demonstrate that the L7/Pcp-2 mRNA is also localized in dendrites of humans [6].
• Using co-immunoprecipitation from COS-7 cells, we found that PCP-2 was only able to interact with Galphai1 but not Galphao nor Galpha-subunits from other families (Galphas, Galphaq, or Galpha12) [4].

Analytical, diagnostic and therapeutic context of PCP2

• Consistently, stalk transplantation experiments suggest that coevolution took place to maintain functional L7/L12 EF-G and P-protein EF-2 couples [5].

References