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EMBO reports 4, 4, 412–418 (2003)
doi:10.1038/sj.embor.embor804
AOP Published online: 14 March 2003
Proteolytic cleavage of PDZD2 generates a secreted peptide containing two PDZ domains
Man-Lung Yeung, Tammy S. M. Tam, Anthony C. C. Tsang & Kwok-Ming Yao
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Department of Biochemistry, Faculty of Medicine, University of Hong Kong, 3/F Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Hong Kong SAR, China
To whom correspondence should be addressed
Kwok-Ming Yao Tel: +852 2819 9275; Fax: +852 2855 1254; kmyao@hkusua.hku.hk
Received 18 November 2002; Accepted 7 February 2003; Published online 14 March 2003.
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Abstract
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.
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