PMID- 11782486
OWN - NLM
STAT- MEDLINE
DCOM- 20020531
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 277
IP  - 17
DP  - 2002 Apr 26
TI  - Regulation of mesangial cell hexokinase activity and expression by 
      heparin-binding epidermal growth factor-like growth factor: epidermal growth 
      factors and phorbol esters increase glucose metabolism via a common mechanism 
      involving classic mitogen-activated protein kinase pathway activation and 
      induction of hexokinase II expression.
PG  - 14370-8
AB  - Heparin-binding epidermal growth factor -like growth factor (HB-EGF) expression 
      and hexokinase (HK) activity are increased in various pathologic renal 
      conditions. Although the mitogenic properties of HB-EGF have been well 
      characterized, its effects on glucose (Glc) metabolism have not. We therefore 
      examined the possibility that HB-EGF might regulate HK activity and expression in 
      glomerular mesangial cells, which constitute the principal renal cell type 
      affected by a variety of pathologic conditions. Protein kinase C (PKC)-dependent 
      classic mitogen-activated protein kinase (MAPK) pathway activation has been 
      associated with increased HK activity in this cell type, so we also examined 
      dependence upon these signaling intermediates. HB-EGF (> or =10 nm) increased 
      total HK activity over 50% within 12-24 h, an effect mimicked by other EGF 
      receptor agonists, but not by IGF-1 or elevated Glc. EGF receptor and classic 
      MAPK pathway antagonists prevented this increase, as did general inhibitors of 
      gene transcription and protein synthesis. Both HB-EGF and phorbol esters 
      activated the classic MAPK pathway, albeit via PKC-independent and PKC-dependent 
      mechanisms, respectively. Both stimuli were associated with increased HK 
      activity, selectively increased HKII isoform expression, and increased Glc 
      metabolism via both the glycolytic-tricarboxylic acid cycle route and the pentose 
      phosphate pathway. HB-EGF thus constitutes a novel regulator of mesangial cell HK 
      activity and Glc metabolism. HKII is the principal regulated isoform in these 
      cells, as it is in insulin-sensitive peripheral tissues, such as muscle. However, 
      the uniform requirement for classic MAPK pathway activation distinguishes HKII 
      regulation in mesangial cells from that observed in muscle. These findings 
      suggest a novel mechanism whereby growth factors may couple metabolism to 
      glomerular injury.
FAU - Robey, R Brooks
AU  - Robey RB
AD  - Department of Medicine, University of Illinois at Chicago College of Medicine, 
      Chicago, Illinois 60612, USA. RBRobey@uic.edu
FAU - Ma, Jianfei
AU  - Ma J
FAU - Santos, Anna V P
AU  - Santos AV
FAU - Noboa, Oscar A
AU  - Noboa OA
FAU - Coy, Platina E
AU  - Coy PE
FAU - Bryson, Jane M
AU  - Bryson JM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20020108
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Hbegf protein, mouse)
RN  - 0 (Heparin-binding EGF-like Growth Factor)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Isoenzymes)
RN  - 0 (Ligands)
RN  - 42HK56048U (Tyrosine)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - IY9XDZ35W2 (Glucose)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Enzyme Induction
MH  - Enzyme Inhibitors/pharmacology
MH  - Epidermal Growth Factor/*physiology
MH  - Flavonoids/pharmacology
MH  - Glomerular Mesangium/*enzymology
MH  - Glucose/*metabolism
MH  - Heparin-binding EGF-like Growth Factor
MH  - Hexokinase/biosynthesis/chemistry/genetics/*metabolism
MH  - Immunohistochemistry
MH  - Insulin-Like Growth Factor I/physiology
MH  - Intercellular Signaling Peptides and Proteins
MH  - Isoenzymes/biosynthesis/chemistry/genetics/metabolism
MH  - Ligands
MH  - *MAP Kinase Signaling System
MH  - Mice
MH  - Oxidation-Reduction
MH  - Phosphorylation
MH  - Protein Kinase C/metabolism
MH  - Tetradecanoylphorbol Acetate/*pharmacology
MH  - Tyrosine/metabolism
EDAT- 2002/01/10 10:00
MHDA- 2002/06/01 10:01
CRDT- 2002/01/10 10:00
PHST- 2002/01/10 10:00 [pubmed]
PHST- 2002/06/01 10:01 [medline]
PHST- 2002/01/10 10:00 [entrez]
AID - S0021-9258(19)60811-2 [pii]
AID - 10.1074/jbc.M111722200 [doi]
PST - ppublish
SO  - J Biol Chem. 2002 Apr 26;277(17):14370-8. doi: 10.1074/jbc.M111722200. Epub 2002 
      Jan 8.