TY - JOUR
T1 - In vivo coupling of insulin-like growth factor II/mannose 6-phosphate receptor to heteromeric G proteins
T2 - Distinct roles of cytoplasmic domains and signal sequestration by the receptor
AU - Ikezu, T.
AU - Okamoto, T.
AU - Giambarella, U.
AU - Yokota, T.
AU - Nishimoto, I.
PY - 1995
Y1 - 1995
N2 - We examined the signaling function of the IGF-II/mannose 6-phosphate receptor (IGF-IIR) by transfecting IGF-IIR cDNAs into COS cells, where adenylyl cyclase (AC) was inhibited by transfection of constitutively activated Gα(i) cDNA (Gα(i2)Q205L). In cells transfected with [GF-IIR cDNA, IGF-II decreased cAMP accumulation promoted by cholera toxin or forskolin. This effect of IGF-II was not observed in untransfected cells or in cells transfected with IGF-IIRs lacking Arg2410-Lys2423. Thus, IGF-IIR, through its cytoplasmic domain, mediates the G(i)-linked action of IGF-II in living cells. We also found that IGF-IIR truncated with C-terminal 28 residues after Ser2424 caused Gβγ-dominant response of AC in response to IGF-II by activating G(i). Comparison with the Gα(i)-dominant response of AC by intact IGF-IIR suggests that the C-terminal 28-residue region inactivates Gβγ. This study not only provides further evidence that IGF- IIR has IGF-II-dependent signaling function to interact with heteromeric G proteins with distinct roles by different cytoplasmic domains, it also suggests that IGF-IIR can separate and sequestrate the Gα and Gβγ signals following G(i) activation.
AB - We examined the signaling function of the IGF-II/mannose 6-phosphate receptor (IGF-IIR) by transfecting IGF-IIR cDNAs into COS cells, where adenylyl cyclase (AC) was inhibited by transfection of constitutively activated Gα(i) cDNA (Gα(i2)Q205L). In cells transfected with [GF-IIR cDNA, IGF-II decreased cAMP accumulation promoted by cholera toxin or forskolin. This effect of IGF-II was not observed in untransfected cells or in cells transfected with IGF-IIRs lacking Arg2410-Lys2423. Thus, IGF-IIR, through its cytoplasmic domain, mediates the G(i)-linked action of IGF-II in living cells. We also found that IGF-IIR truncated with C-terminal 28 residues after Ser2424 caused Gβγ-dominant response of AC in response to IGF-II by activating G(i). Comparison with the Gα(i)-dominant response of AC by intact IGF-IIR suggests that the C-terminal 28-residue region inactivates Gβγ. This study not only provides further evidence that IGF- IIR has IGF-II-dependent signaling function to interact with heteromeric G proteins with distinct roles by different cytoplasmic domains, it also suggests that IGF-IIR can separate and sequestrate the Gα and Gβγ signals following G(i) activation.
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U2 - 10.1074/jbc.270.49.29224
DO - 10.1074/jbc.270.49.29224
M3 - Article
C2 - 7493951
AN - SCOPUS:0028788172
VL - 270
SP - 29224
EP - 29228
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 49
ER -