Proteolytic cleavage of PDZD2 generates a secreted peptide containing two PDZ domains.
PDZD2 (PDZ-domain-containing 2; also known as PAPIN, AIPC and PIN1) is a ubiquitously expressed multi-PDZ-domain protein. We have shown that PDZD2, which shows extensive homology to pro-interleukin-16 (pro-IL-16), is localized mainly to the endoplasmic reticulum (ER). Pro-IL-16 is cleaved in a caspase-3-dependent mechanism to generate the secreted cytokine IL-16. The abundant expression of PDZD2 in the ER, and its sequence similarity to pro-IL-16, suggests that similar post-translational processing of PDZD2 may occur. Indeed, western blotting and mass spectrometry analysis of conditioned medium from cells transfected with epitope-tagged PDZD2 show that there is secretion of a PDZD2 peptide of approximately 37 kDa (sPDZD2, for secreted PDZD2) that contains two PDZ domains. Expression of PDZD2 was detected in several tissues. Furthermore, sPDZD2 secretion is suppressed by the mutation of a sequence that shows similarity to caspase recognition motifs or by treatment with a caspase inhibitor. In summary, PDZD2 is the first reported multi-PDZ protein that is processed by proteolytic cleavage to generate a secreted peptide containing two PDZ domains.
Yeung
Man-Lung
ML
Department of Biochemistry, Faculty of Medicine, University of Hong Kong, Hong Kong, China.
Tam
Tammy S M
TS
Tsang
Anthony C C
AC
Yao
Kwok-Ming
KM
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules; D002460:Cell Line; D017077:Culture Media, Conditioned; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007668:Kidney / Q000378:metabolism; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D009363:Neoplasm Proteins; C423943:PDZD2 protein, human; C414604:PDZD2 protein, rat; D011994:Recombinant Proteins