PMID- 8294430
OWN - NLM
STAT- MEDLINE
DCOM- 19940225
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 269
IP  - 3
DP  - 1994 Jan 21
TI  - Phosphorylation of serine 985 negatively regulates the hepatocyte growth factor 
      receptor kinase.
PG  - 1815-20
AB  - The receptor for hepatocyte growth factor/scatter factor (HGF/SF) is an alpha 
      beta tyrosine kinase of 190 kDa which mediates growth and motility in several 
      cell types. We have previously shown that tyrosine autophosphorylation enhances 
      the receptor kinase activity, while serine phosphorylation by protein kinase C or 
      other Ca(2+)-dependent kinase(s) is inhibitory. We now identify Ser985 as the 
      major phosphorylation site for the protein kinases responsible for such 
      inhibition. Both phorbol esters or Ca2+ ionophore treatment induces 
      phosphorylation of the same tryptic phosphopeptide corresponding to the sequence 
      Leu983-Arg987 located in the juxta-membrane domain of the receptor beta chain. 
      Purified protein kinase C phosphorylates in vitro a synthetic peptide (V14S) 
      including Ser985. Trypsin digestion of the phosphorylated V14S generates a single 
      phosphopeptide comigrating in reverse-phase high performance liquid 
      chromatography with the tryptic peptide phosphorylated in vivo. Phorbol ester 
      treatment of cultured cells inhibits the ligand-induced tyrosine 
      autophosphorylation of the receptor. In vitro, Ser985 phosphorylation inhibits 
      the receptor tyrosine kinase activity on exogenous substrates. Substitution of 
      Ser985 by site-directed mutagenesis results in increased tyrosine phosphorylation 
      of the receptor and abolishes down-modulation by protein kinase C. These data 
      show that phosphorylation of Ser985 is a key mechanism for the negative 
      regulation of HGF/SF receptor.
FAU - Gandino, L
AU  - Gandino L
AD  - Department of Biomedical Sciences and Oncology, University of Torino Medical 
      School, Italy.
FAU - Longati, P
AU  - Longati P
FAU - Medico, E
AU  - Medico E
FAU - Prat, M
AU  - Prat M
FAU - Comoglio, P M
AU  - Comoglio PM
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Peptide Fragments)
RN  - 0 (Phosphates)
RN  - 0 (Phosphopeptides)
RN  - 37H9VM9WZL (Calcimycin)
RN  - 452VLY9402 (Serine)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
GS  - MET
MH  - Amino Acid Sequence
MH  - Calcimycin/pharmacology
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism
MH  - Cell Line
MH  - Consensus Sequence
MH  - Hepatocyte Growth Factor/metabolism
MH  - Humans
MH  - Kinetics
MH  - Molecular Sequence Data
MH  - Peptide Fragments/chemistry/isolation & purification
MH  - Phosphates/metabolism
MH  - Phosphopeptides/chemistry/isolation & purification
MH  - Phosphorylation
MH  - Protein Kinase C/*metabolism
MH  - Proto-Oncogene Proteins c-met
MH  - Proto-Oncogenes
MH  - Receptor Protein-Tyrosine Kinases/*metabolism
MH  - Sequence Homology, Amino Acid
MH  - *Serine
MH  - Stomach Neoplasms
MH  - Substrate Specificity
MH  - Tetradecanoylphorbol Acetate/*pharmacology
MH  - Tumor Cells, Cultured
EDAT- 1994/01/21 00:00
MHDA- 1994/01/21 00:01
CRDT- 1994/01/21 00:00
PHST- 1994/01/21 00:00 [pubmed]
PHST- 1994/01/21 00:01 [medline]
PHST- 1994/01/21 00:00 [entrez]
AID - S0021-9258(17)42099-0 [pii]
PST - ppublish
SO  - J Biol Chem. 1994 Jan 21;269(3):1815-20.