PMID- 10454588
OWN - NLM
STAT- MEDLINE
DCOM- 19990910
LR  - 20210526
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 9
DP  - 1999 Sep
TI  - Functional analysis of H-Ryk, an atypical member of the receptor tyrosine kinase 
      family.
PG  - 6427-40
AB  - H-Ryk is an atypical receptor tyrosine kinase which differs from other members of
      this family at a number of conserved residues in the activation and nucleotide
      binding domains. Using a chimeric receptor approach, we demonstrate that H-Ryk
      has impaired catalytic activity. Despite the receptor's inability to undergo
      autophosphorylation or phosphorylate substrates, we demonstrate that ligand
      stimulation of the chimeric receptor results in activation of the
      mitogen-activated protein kinase pathway. The ability to transduce signals is
      abolished by mutation of the invariant lysine (K334A) in subdomain II of H-Ryk.
      Further, by in vitro mutagenesis, we show that the amino acid substitutions in
      the activation domain of H-Ryk account for the loss of catalytic activity. In
      addition to the essential aspartate residue, either phenylalanine or glycine is
      required in the activation domain to maintain proper conformation of the
      catalytic domain and thus ensure receptor autophosphorylation. Homology modelling
      of the catalytic domain of H-Ryk provides a rationale for these findings. Thus,
      the signalling properties of H-Ryk are divergent from those of other classical
      receptor tyrosine kinases.
FAU - Katso, R M
AU  - Katso RM
AD  - Molecular Oncology Laboratories, Imperial Cancer Research Fund, Institute of
      Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United
      Kingdom.
FAU - Russell, R B
AU  - Russell RB
FAU - Ganesan, T S
AU  - Ganesan TS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (DNA Primers)
RN  - 0 (Ligands)
RN  - 0 (Recombinant Fusion Proteins)
RN  - EC 2.7.10.1 (RYK protein, human)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Animals
MH  - Base Sequence
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism
MH  - Catalytic Domain/genetics
MH  - Cell Line, Transformed
MH  - DNA Primers/genetics
MH  - Enzyme Activation
MH  - Humans
MH  - Ligands
MH  - Mice
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Phosphorylation
MH  - Point Mutation
MH  - Protein Conformation
MH  - Receptor Protein-Tyrosine Kinases/genetics/*metabolism
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Sequence Homology, Amino Acid
MH  - Signal Transduction
PMC - PMC84612
EDAT- 1999/08/24 00:00
MHDA- 1999/08/24 00:01
CRDT- 1999/08/24 00:00
PHST- 1999/08/24 00:00 [pubmed]
PHST- 1999/08/24 00:01 [medline]
PHST- 1999/08/24 00:00 [entrez]
AID - 10.1128/MCB.19.9.6427 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 Sep;19(9):6427-40. doi: 10.1128/MCB.19.9.6427.