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While\n                    <jats:italic>PKD1<\/jats:italic>\n                    encodes a large integral membrane protein containing several structural motifs found in known proteins involved in cell\u2013cell or cell\u2013matrix interactions, PKD2 has homology to PKD1 and the major subunit of the voltage-activated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channels. We now describe sequence homology between PKD2 and various members of the mammalian transient receptor potential channel (TRPC) proteins, thought to be activated by G protein-coupled receptor activation and\/or depletion of internal Ca\n                    <jats:sup>2+<\/jats:sup>\n                    stores. We show that PKD2 can directly associate with TRPC1 but not TRPC3 in transfected cells and\n                    <jats:italic>in vitro<\/jats:italic>\n                    . This association is mediated by two distinct domains in PKD2. One domain involves a minimal region of 73 amino acids in the C-terminal cytoplasmic tail of PKD2 shown previously to constitute an interacting domain with PKD1. However, distinct residues within this region mediate specific interactions with TRPC1 or PKD1. The C-terminal domain is sufficient but not necessary for the PKD2\u2013TRPC1 association. A more N-terminal domain located within transmembrane segments S2 and S5, including a putative pore helical region between S5 and S6, is also responsible for the association. Given the ability of the TRPC to form functional homo- and heteromultimeric complexes, these data provide evidence that PKD2 may be functionally related to TRPC proteins and suggest a possible role of PKD2 in modulating Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry in response to G protein-coupled receptor activation and\/or store depletion.\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.7.3934","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:42:40Z","timestamp":1027680160000},"page":"3934-3939","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":262,"title":["Specific association of the gene product of\n                    <i>PKD2<\/i>\n                    with the TRPC1 channel"],"prefix":"10.1073","volume":"96","author":[{"given":"Leonidas","family":"Tsiokas","sequence":"first","affiliation":[{"name":"Renal Division, RW 563, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215; and Laboratory of Molecular and Developmental Neuroscience, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Arnould","sequence":"additional","affiliation":[{"name":"Renal Division, RW 563, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215; and Laboratory of Molecular and Developmental Neuroscience, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenwen","family":"Zhu","sequence":"additional","affiliation":[{"name":"Renal Division, RW 563, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215; and Laboratory of Molecular and Developmental Neuroscience, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Kim","sequence":"additional","affiliation":[{"name":"Renal Division, RW 563, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215; and Laboratory of Molecular and Developmental Neuroscience, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Walz","sequence":"additional","affiliation":[{"name":"Renal Division, RW 563, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215; and Laboratory of Molecular and Developmental Neuroscience, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikas P.","family":"Sukhatme","sequence":"additional","affiliation":[{"name":"Renal Division, RW 563, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215; and Laboratory of Molecular and Developmental Neuroscience, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1999,3,30]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1056\/NEJM199307293290508","volume":"329","author":"Gabow P A","year":"1993","unstructured":"P A Gabow N Engl J Med 329, 332\u2013342 (1993).","journal-title":"N Engl J Med"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/0092-8674(94)90137-6","volume":"77","year":"1994","unstructured":"Cell 77, 881\u2013894 (1994).","journal-title":"Cell"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/0092-8674(95)90339-9","volume":"81","year":"1995","unstructured":"Cell 81, 289\u2013298 (1995).","journal-title":"Cell"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1126\/science.272.5266.1339","volume":"272","author":"Mochizuki T","year":"1996","unstructured":"T Mochizuki, G Wu, T Hayashi, S L Xenophontos, B Veldhuisen, J J Saris, D M Reynolds, Y Cai, P A Gabow, A Pierides, et al. 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