The Ca2+-dependent lipid binding domain of P120(GAP) mediates protein-protein interactions with Ca2+-dependent membrane-binding proteins

Evidence for a direct interaction between annexin VI and P120(GAP)

A J Davis, Jonathan Delafield-Butt, J H Walker, S E Moss, D J Gawler

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Abstract

The CaLB domain is a 43-amino acid sequence motif found in a number of functionally diverse signaling proteins including three Ras-specific GTPase activating proteins (GAPs), In the Ras GTPase activating protein, p120(GAP), this domain has the ability to confer membrane association in response to intracellular Ca2+ elevation, Here we have isolated three proteins, p55, p70, and p120, which interact with the p120(GAP) CaLB domain in vitro. We identify p70 as the Ca2+-dependent phospholipid-binding protein annexin VI, Using co-immunoprecipitation studies, we have shown that the interaction between p120(GAP) and annexin VI is also detectable in rat fibroblasts, suggesting that this interaction may have a physiological role in vivo. Thus, the CaLB domain in p120(GAP) appears to have the ability to direct specific protein-protein interactions with Ca2+-dependent membrane-associated proteins, In addition, annexin VI is known to have tumor suppressor activity, Therefore, it is possible that the interaction of annexin VI with p120(GAP) may be important in the subsequent modulation of p21(ras) activity.

Original languageEnglish
Pages (from-to)24333-24336
Number of pages4
JournalJournal of Biological Chemistry
Volume271
DOIs
Publication statusPublished - 4 Oct 1996

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p120 GTPase Activating Protein
Annexin A6
Carrier Proteins
Membrane Proteins
ras GTPase-Activating Proteins
Membranes
Lipids
Proteins
Proto-Oncogene Proteins p21(ras)
GTPase-Activating Proteins
Amino Acid Motifs
Fibroblasts
Immunoprecipitation
Rats
Tumors
Amino Acid Sequence
Phospholipids
Modulation
Amino Acids
Neoplasms

Keywords

  • signaling proteins
  • membrane-binding proteins

Cite this

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title = "The Ca2+-dependent lipid binding domain of P120(GAP) mediates protein-protein interactions with Ca2+-dependent membrane-binding proteins: Evidence for a direct interaction between annexin VI and P120(GAP)",
abstract = "The CaLB domain is a 43-amino acid sequence motif found in a number of functionally diverse signaling proteins including three Ras-specific GTPase activating proteins (GAPs), In the Ras GTPase activating protein, p120(GAP), this domain has the ability to confer membrane association in response to intracellular Ca2+ elevation, Here we have isolated three proteins, p55, p70, and p120, which interact with the p120(GAP) CaLB domain in vitro. We identify p70 as the Ca2+-dependent phospholipid-binding protein annexin VI, Using co-immunoprecipitation studies, we have shown that the interaction between p120(GAP) and annexin VI is also detectable in rat fibroblasts, suggesting that this interaction may have a physiological role in vivo. Thus, the CaLB domain in p120(GAP) appears to have the ability to direct specific protein-protein interactions with Ca2+-dependent membrane-associated proteins, In addition, annexin VI is known to have tumor suppressor activity, Therefore, it is possible that the interaction of annexin VI with p120(GAP) may be important in the subsequent modulation of p21(ras) activity.",
keywords = "signaling proteins, membrane-binding proteins",
author = "Davis, {A J} and Jonathan Delafield-Butt and Walker, {J H} and Moss, {S E} and Gawler, {D J}",
year = "1996",
month = "10",
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doi = "10.1074/jbc.271.40.24333",
language = "English",
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TY - JOUR

T1 - The Ca2+-dependent lipid binding domain of P120(GAP) mediates protein-protein interactions with Ca2+-dependent membrane-binding proteins

T2 - Evidence for a direct interaction between annexin VI and P120(GAP)

AU - Davis, A J

AU - Delafield-Butt, Jonathan

AU - Walker, J H

AU - Moss, S E

AU - Gawler, D J

PY - 1996/10/4

Y1 - 1996/10/4

N2 - The CaLB domain is a 43-amino acid sequence motif found in a number of functionally diverse signaling proteins including three Ras-specific GTPase activating proteins (GAPs), In the Ras GTPase activating protein, p120(GAP), this domain has the ability to confer membrane association in response to intracellular Ca2+ elevation, Here we have isolated three proteins, p55, p70, and p120, which interact with the p120(GAP) CaLB domain in vitro. We identify p70 as the Ca2+-dependent phospholipid-binding protein annexin VI, Using co-immunoprecipitation studies, we have shown that the interaction between p120(GAP) and annexin VI is also detectable in rat fibroblasts, suggesting that this interaction may have a physiological role in vivo. Thus, the CaLB domain in p120(GAP) appears to have the ability to direct specific protein-protein interactions with Ca2+-dependent membrane-associated proteins, In addition, annexin VI is known to have tumor suppressor activity, Therefore, it is possible that the interaction of annexin VI with p120(GAP) may be important in the subsequent modulation of p21(ras) activity.

AB - The CaLB domain is a 43-amino acid sequence motif found in a number of functionally diverse signaling proteins including three Ras-specific GTPase activating proteins (GAPs), In the Ras GTPase activating protein, p120(GAP), this domain has the ability to confer membrane association in response to intracellular Ca2+ elevation, Here we have isolated three proteins, p55, p70, and p120, which interact with the p120(GAP) CaLB domain in vitro. We identify p70 as the Ca2+-dependent phospholipid-binding protein annexin VI, Using co-immunoprecipitation studies, we have shown that the interaction between p120(GAP) and annexin VI is also detectable in rat fibroblasts, suggesting that this interaction may have a physiological role in vivo. Thus, the CaLB domain in p120(GAP) appears to have the ability to direct specific protein-protein interactions with Ca2+-dependent membrane-associated proteins, In addition, annexin VI is known to have tumor suppressor activity, Therefore, it is possible that the interaction of annexin VI with p120(GAP) may be important in the subsequent modulation of p21(ras) activity.

KW - signaling proteins

KW - membrane-binding proteins

U2 - 10.1074/jbc.271.40.24333

DO - 10.1074/jbc.271.40.24333

M3 - Article

VL - 271

SP - 24333

EP - 24336

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

ER -