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J. Biol. Chem., Vol. 277, Issue 20, 18084-18090, May 17, 2002

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Unusual Alternative Splicing within the Human Kallikrein Genes KLK2 and KLK3 Gives Rise to Novel Prostate-specific Proteins^*

Anat David^§, Nicola Mabjeesh^¶, Idit Azar^§, Sharon Biton^§, Sharon Engel, Jeanne Bernstein, Jacob Romano, Yoav Avidor^¶, Tova Waks, Zelig Eshhar, Salomon Z. Langer, Beatriz Lifschitz-Mercer^**, Haim Matzkin^¶, Galit Rotman, Amir Toporik, Kinneret Savitsky, and Liat Mintz^§§

From  Compugen Ltd., 72 Pinchas Rosen St., Tel Aviv 69512, the  Department of Immunology, Weizmann Institute of Science, Rehovot 76100, the ^¶ Department of Urology and the ^** Department of Pathology, Tel Aviv Sourasky Medical Center, 6 Weizmann St., Tel Aviv 64239, Israel, and ^§§ Compugen Inc., Jamesburg, New Jersey 08831

Prostate-specific antigen (PSA) and human kallikrein 2 are closely related products of the human kallikrein genes KLK3 and KLK2, respectively. Both PSA and human kallikrein 2 are produced and secreted in the prostate and have important applications in the diagnosis of prostate cancer. We report here the identification of unusual mRNA splice variants of the KLK2 and KLK3 genes that result from inclusion of intronic sequences adjacent to the first exon. The novel proteins encoded by these transcripts, named PSA-linked molecule (PSA-LM) and hK2-linked molecule (K-LM), share only the signal peptide with the original protein product of the respective gene. The mature proteins are entirely different and bear no similarity to the kallikrein family or to other proteins in the databases. As is the case with PSA, PSA-LM is expressed in the secretory epithelial cells of the prostate and is up-regulated in response to androgenic stimulation. A similar pattern of expression is suggested for K-LM.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AF335478, AF335477, and AF336106.

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