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The Proximity Ligation Assay\n                    <jats:sup>\u00ae<\/jats:sup>\n                    (PLA) offers the opportunity to visualize the subcellular location of such interactions at endogenous protein levels, provided that the probes that recognize the target proteins are within 40 nm. This sensitive technique not only elucidates protein\u2010protein interactions, but also can reveal post\u2010translational protein modifications. The technique is useful even in cases where material is limited, such as when paraffin\u2010embedded clinical specimens are the only available material, as well as after experimental intervention in 2D and 3D model systems. Here we describe the basic protocol for using the commercially available Proximity Ligation Assay\u2122 materials (Sigma\u2010Aldrich, St. Louis, MO), and incorporate details to aid the researcher in successfully performing the experiments. \u00a9 2020 Wiley Periodicals LLC.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Basic Protocol 1<\/jats:bold>\n                    : Proximity ligation assay\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Support Protocol 1<\/jats:bold>\n                    : Antigen retrieval method for formalin\u2010fixed, paraffin\u2010embedded tissues\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Support Protocol 2<\/jats:bold>\n                    : Creation of custom PLA probes using the Duolink\u2122 In Situ Probemaker Kit when commercially available probes are not suitable\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Basic Protocol 2<\/jats:bold>\n                    : Imaging, quantification, and analysis of PLA signals\n                  <\/jats:p>","DOI":"10.1002\/cpcb.115","type":"journal-article","created":{"date-parts":[[2020,10,12]],"date-time":"2020-10-12T14:18:29Z","timestamp":1602512309000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":163,"title":["Proximity Ligation Assay for Detecting Protein\u2010Protein Interactions and Protein Modifications in Cells and Tissues in Situ"],"prefix":"10.1002","volume":"89","author":[{"given":"Marihan","family":"Hegazy","sequence":"first","affiliation":[{"name":"Department of Pathology Northwestern University Feinberg School of Medicine  Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eran","family":"Cohen\u2010Barak","sequence":"additional","affiliation":[{"name":"Department of Dermatology Emek Medical Center  Afula 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