Literature summary for 2.7.4.21 extracted from

Niger, C.; Luciotti, M.A.; Buo, A.M.; Hebert, C.; Ma, V.; Stains, J.P.
The regulation of runt-related transcription factor 2 by fibroblast growth factor-2 and connexin43 requires the inositol polyphosphate/protein kinase Cdelta cascade (2013), J. Bone Miner. Res., 28, 1468-1477.

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Cloned(Commentary)

Cloned (Comment)	Organism
gene ip6k1, quantitative real-time PCr enzyme expression analysis	Mus musculus
gene ip6k2, quantitative real-time PCr enzyme expression analysis	Mus musculus
gene ip6k3, quantitative real-time PCr enzyme expression analysis	Mus musculus

Inhibitors

Inhibitors	Comment	Organism	Structure
N2-(3-trifluorobenzyl)-N6-(4-nitrobenzyl)purine	a selective inhibitor, abolishes the basal and Cx43-potentiated Runx2 activity in response to FGF2 treatment relative to DMSO treated controls; a selective inhibitor, abolishes the basal and Cx43-potentiated Runx2 activity in response to FGF2 treatment relative to DMSO treated controls	Mus musculus
N2-(m-(trifluoromethyl) benzyl) N6-(p-nitrobenzyl) purine	TNP, a selective inhibitor, abolishes the basal and Cx43-potentiated Runx2 activity in response to FGF2 treatment relative to DMSO treated controls	Mus musculus

Organism

Organism	UniProt	Comment	Textmining
Mus musculus	Q6PD10	isozyme IP6K1	-
Mus musculus	Q80V72	isozyme IP6K2	-
Mus musculus	Q8BWD2	isozyme IP6K3	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
MC-3T3 cell	MC-3T3 osteoblasts express IP6K1 and IP6K2 mRNA more than 25fold more abundantly than IP6K3	Mus musculus	-
MC-3T3 cell	MC3T3 osteoblasts express IP6K1 and IP6K2 mRNA more than 25fold more abundantly than IP6K3	Mus musculus	-
osteoblast	-	Mus musculus	-
osteocyte	-	Mus musculus	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
additional information	the enzyme generates inositol 1,3,4,5-tetrakisphosphate (InsP4) and InsP5	Mus musculus	?	-	?

Synonyms

Synonyms	Comment	Organism
inositol hexakisphosphate kinase 1	-	Mus musculus
inositol hexakisphosphate kinase 2	-	Mus musculus
inositol hexakisphosphate kinase 3	-	Mus musculus
IP6K1	-	Mus musculus
IP6K2	-	Mus musculus
IP6K3	-	Mus musculus

General Information

General Information	Comment	Organism
malfunction	analysis of the impact of siRNA-mediated knockdown of the two more abundant IP6Ks on Runx2 transcriptional activity. Knockdown of IP6K1 inhibits the FGF2-induced Runx2 activity, both basally and in response to Cx43 overexpression, more potently than knockdown of IP6K2. Knockdown of expression and/or inhibition of function of phospholipase Cgamma1, inositol polyphosphate multikinase, which generates inositol 1,3,4,5-tetrakisphosphate (InsP4) and InsP5, and inositol hexakisphosphate kinase 1/2, which generates inositol pyrophosphates, prevented the ability of Cx43 to potentiate FGF2 induced signaling through Runx2. Overexpression of phospholipase Cgamma1 and inositol hexakisphosphate kinase 1/2 enhances FGF2 activation of Runx2 and the effect of Cx43 overexpression on this response. Enzyme inhibition by TNP abolishes the basal and Cx43-potentiated Runx2 activity in response to FGF2 treatment relative to DMSO treated controls	Mus musculus
malfunction	analysis of the impact of siRNA-mediated knockdown of the two more abundant IP6Ks on Runx2 transcriptional activity. Knockdown of IP6K1 inhibits the FGF2-induced Runx2 activity, both basally and in response to Cx43 overexpression, more potently than knockdown of IP6K2Knockdown of expression and/or inhibition of function of phospholipase Cgamma1, inositol polyphosphate multikinase, which generates inositol 1,3,4,5-tetrakisphosphate (InsP4) and InsP5, and inositol hexakisphosphate kinase 1/2, which generates inositol pyrophosphates, prevented the ability of Cx43 to potentiate FGF2 induced signaling through Runx2. Overexpression of phospholipase Cgamma1 and inositol hexakisphosphate kinase 1/2 enhances FGF2 activation of Runx2 and the effect of Cx43 overexpression on this response. Enzyme inhibition by TNP abolishes the basal and Cx43-potentiated Runx2 activity in response to FGF2 treatment relative to DMSO treated controls	Mus musculus
malfunction	knockdown of expression and/or inhibition of function of phospholipase Cgamma1, inositol polyphosphate multikinase, which generates inositol 1,3,4,5-tetrakisphosphate (InsP4) and InsP5, and inositol hexakisphosphate kinase 1/2, which generates inositol pyrophosphates, prevented the ability of Cx43 to potentiate FGF2 induced signaling through Runx2. Overexpression of phospholipase Cgamma1 and inositol hexakisphosphate kinase 1/2 enhances FGF2 activation of Runx2 and the effect of Cx43 overexpression on this response. Enzyme inhibition by TNP abolishes the basal and Cx43-potentiated Runx2 activity in response to FGF2 treatment relative to DMSO treated controls	Mus musculus
metabolism	the enzyme is involved in the phospholipase Cgamma1/inositol polyphosphate/protein kinase C delta (PKCd) cascade which contributes to the Cx43-dependent transcriptional response of MC3T3 osteoblasts to FGF2. FGF2-signaling involves the inositol polyphosphate cascade, including inositol hexakisphosphate kinase (IP6K). FGF2 is an important regulator of skeletal tissue with complex action, acting at several stages of differentiation to differentially affect osteoblast function. Molecular mechanisms by which inositol diphosphates impact signaling in osteoblastic cells, overview	Mus musculus
physiological function	IP6K regulates Runx2 and osteoblast gene expression	Mus musculus
physiological function	IP6K regulates Runx2 and osteoblast gene expression. The nuclear translocation and association of PKCdelta with Runx2 is dependent upon IP6K1	Mus musculus

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Release 2023.1 (January 2023)