The isolated polycystin-1 COOH-terminal can activate or block polycystin-1 signaling

Uma Basavanna, Kimberly M. Weber, Qinghua Hu, Roy Ziegelstein, Gregory G. Germino, Michael Sutters

Research output: Contribution to journalArticle

Abstract

Much of what is known of the activities of polycystin-1 has been inferred from the effects of the isolated cytoplasmic COOH-terminal domain, but it is not clear whether the truncation acts like polycystin-1, as a dominant negative, or in unrelated pathways. To address this question, we have examined functional interactions between the intact and truncated forms of polycystin-1 in one cell system. In cells expressing only native polycystin-1, introduction of the truncation replicated the activity of the full-length protein. Conversely, when background levels of polycystin-1 were modestly elevated, the truncation acted as a dominant negative. Hence, the truncation acts in the polycystin pathway, but with effects that depend upon the background level of polycystin-1 expression. Our data raise the possibility that the cytoplasmic carboxyl terminus, either through cleavage products or intramolecular interactions, might feed back to modulate the activity of parent or intact polycystin-1.

Original languageEnglish (US)
Pages (from-to)367-372
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume359
Issue number2
DOIs
StatePublished - Jul 27 2007

Fingerprint

TRPP Cation Channels
polycystic kidney disease 1 protein
Cells
Feedback
Proteins

Keywords

  • Apoptosis
  • Autosomal dominant polycystic kidney disease
  • Cell calcium
  • Endoplasmic reticulum
  • Polycystin-1
  • Proliferation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

The isolated polycystin-1 COOH-terminal can activate or block polycystin-1 signaling. / Basavanna, Uma; Weber, Kimberly M.; Hu, Qinghua; Ziegelstein, Roy; Germino, Gregory G.; Sutters, Michael.

In: Biochemical and Biophysical Research Communications, Vol. 359, No. 2, 27.07.2007, p. 367-372.

Research output: Contribution to journalArticle

Basavanna, Uma ; Weber, Kimberly M. ; Hu, Qinghua ; Ziegelstein, Roy ; Germino, Gregory G. ; Sutters, Michael. / The isolated polycystin-1 COOH-terminal can activate or block polycystin-1 signaling. In: Biochemical and Biophysical Research Communications. 2007 ; Vol. 359, No. 2. pp. 367-372.
@article{51b6998c3b7a4d61814a14dd3c9b3942,
title = "The isolated polycystin-1 COOH-terminal can activate or block polycystin-1 signaling",
abstract = "Much of what is known of the activities of polycystin-1 has been inferred from the effects of the isolated cytoplasmic COOH-terminal domain, but it is not clear whether the truncation acts like polycystin-1, as a dominant negative, or in unrelated pathways. To address this question, we have examined functional interactions between the intact and truncated forms of polycystin-1 in one cell system. In cells expressing only native polycystin-1, introduction of the truncation replicated the activity of the full-length protein. Conversely, when background levels of polycystin-1 were modestly elevated, the truncation acted as a dominant negative. Hence, the truncation acts in the polycystin pathway, but with effects that depend upon the background level of polycystin-1 expression. Our data raise the possibility that the cytoplasmic carboxyl terminus, either through cleavage products or intramolecular interactions, might feed back to modulate the activity of parent or intact polycystin-1.",
keywords = "Apoptosis, Autosomal dominant polycystic kidney disease, Cell calcium, Endoplasmic reticulum, Polycystin-1, Proliferation",
author = "Uma Basavanna and Weber, {Kimberly M.} and Qinghua Hu and Roy Ziegelstein and Germino, {Gregory G.} and Michael Sutters",
year = "2007",
month = "7",
day = "27",
doi = "10.1016/j.bbrc.2007.05.114",
language = "English (US)",
volume = "359",
pages = "367--372",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - The isolated polycystin-1 COOH-terminal can activate or block polycystin-1 signaling

AU - Basavanna, Uma

AU - Weber, Kimberly M.

AU - Hu, Qinghua

AU - Ziegelstein, Roy

AU - Germino, Gregory G.

AU - Sutters, Michael

PY - 2007/7/27

Y1 - 2007/7/27

N2 - Much of what is known of the activities of polycystin-1 has been inferred from the effects of the isolated cytoplasmic COOH-terminal domain, but it is not clear whether the truncation acts like polycystin-1, as a dominant negative, or in unrelated pathways. To address this question, we have examined functional interactions between the intact and truncated forms of polycystin-1 in one cell system. In cells expressing only native polycystin-1, introduction of the truncation replicated the activity of the full-length protein. Conversely, when background levels of polycystin-1 were modestly elevated, the truncation acted as a dominant negative. Hence, the truncation acts in the polycystin pathway, but with effects that depend upon the background level of polycystin-1 expression. Our data raise the possibility that the cytoplasmic carboxyl terminus, either through cleavage products or intramolecular interactions, might feed back to modulate the activity of parent or intact polycystin-1.

AB - Much of what is known of the activities of polycystin-1 has been inferred from the effects of the isolated cytoplasmic COOH-terminal domain, but it is not clear whether the truncation acts like polycystin-1, as a dominant negative, or in unrelated pathways. To address this question, we have examined functional interactions between the intact and truncated forms of polycystin-1 in one cell system. In cells expressing only native polycystin-1, introduction of the truncation replicated the activity of the full-length protein. Conversely, when background levels of polycystin-1 were modestly elevated, the truncation acted as a dominant negative. Hence, the truncation acts in the polycystin pathway, but with effects that depend upon the background level of polycystin-1 expression. Our data raise the possibility that the cytoplasmic carboxyl terminus, either through cleavage products or intramolecular interactions, might feed back to modulate the activity of parent or intact polycystin-1.

KW - Apoptosis

KW - Autosomal dominant polycystic kidney disease

KW - Cell calcium

KW - Endoplasmic reticulum

KW - Polycystin-1

KW - Proliferation

UR - http://www.scopus.com/inward/record.url?scp=34249939064&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34249939064&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2007.05.114

DO - 10.1016/j.bbrc.2007.05.114

M3 - Article

C2 - 17540339

AN - SCOPUS:34249939064

VL - 359

SP - 367

EP - 372

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 2

ER -