Interaction of prostate specific membrane antigen with clathrin and the adaptor protein complex-2

  • Authors:
    • Oscar B. Goodman
    • Sonali P. Barwe
    • Brigitte Ritter
    • Peter S. McPherson
    • Ann-Jeanette Vasko
    • James H. Keen
    • David M. Nanus
    • Neil H. Bander
    • Ayyappan K. Rajasekaran
  • View Affiliations

  • Published online on: November 1, 2007     https://doi.org/10.3892/ijo.31.5.1199
  • Pages:1199-1203
0

Abstract

Prostate-specific membrane antigen (PSMA) is an integral membrane glycoprotein expressed in prostatic epithelia and is being evaluated as a therapeutic target in prostate cancer. It undergoes constitutive receptor-mediated endocytosis via clathrin-coated pits, which is enhanced in the presence of monoclonal antibodies directed against it. We describe distinct interactions of PSMA with clathrin and the clathrin adaptor protein-2 (AP-2) complex, two components of clathrin-coated pits. The intracellular N-terminal domain of PSMA interacts with the N-terminal globular domain of clathrin heavy chain. Deletion analysis revealed an important determinant of this interaction residing within the proximal portion of the clathrin heavy chain N-terminal domain (amino acids 1-85) distinct from the clathrin binding sites of other known clathrin-binding proteins. Furthermore, PSMA interacts with the ear domain of α-adaptin (an AP-2 subunit), and a glutamic acid residue at position 7 in the cytoplasmic tail of PSMA is essential for this interaction. These data indicate that PSMA exhibits a high affinity, specific association with the clathrin-based endocytic machinery by distinct interactions with both clathrin and AP-2. Thus, although PSMA is a new member of the dual AP and clathrin binding proteins, its α-adaptin and clathrin heavy chain binding determinants are distinct from those of other members.

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November 2007
Volume 31 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

2015 Impact Factor: 3.018
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APA
Goodman, O.B., Barwe, S.P., Ritter, B., McPherson, P.S., Vasko, A., Keen, J.H. ... Rajasekaran, A.K. (2007). Interaction of prostate specific membrane antigen with clathrin and the adaptor protein complex-2. International Journal of Oncology, 31, 1199-1203. https://doi.org/10.3892/ijo.31.5.1199
MLA
Goodman, O. B., Barwe, S. P., Ritter, B., McPherson, P. S., Vasko, A., Keen, J. H., Nanus, D. M., Bander, N. H., Rajasekaran, A. K."Interaction of prostate specific membrane antigen with clathrin and the adaptor protein complex-2". International Journal of Oncology 31.5 (2007): 1199-1203.
Chicago
Goodman, O. B., Barwe, S. P., Ritter, B., McPherson, P. S., Vasko, A., Keen, J. H., Nanus, D. M., Bander, N. H., Rajasekaran, A. K."Interaction of prostate specific membrane antigen with clathrin and the adaptor protein complex-2". International Journal of Oncology 31, no. 5 (2007): 1199-1203. https://doi.org/10.3892/ijo.31.5.1199