PMID- 10066823
OWN - NLM
STAT- MEDLINE
DCOM- 19990413
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 11
DP  - 1999 Mar 12
TI  - Molecular features underlying the sequential phosphorylation of HS1 protein and
      its association with c-Fgr protein-tyrosine kinase.
PG  - 7557-64
AB  - The hematopoietic lineage cell-specific protein HS1 was shown to undergo a
      process of sequential phosphorylation both in vitro and in vivo, which is
      synergistically mediated by Syk and Src family protein-tyrosine kinases and
      essential for B cell antigen receptor-mediated apoptosis. We have now identified 
      tyrosine 222 as the HS1 residue phosphorylated by the Src family protein kinases 
      c-Fgr and Lyn, and we show that a truncated form of HS1 (HS1-208-401) lacking the
      N-terminal putative DNA binding region and the C-terminal Src homology 3 (SH3)
      domain is still able to undergo all the steps of sequential phosphorylation as
      efficiently as full-length HS1. We also show that a stable association of
      phospho-HS1 with c-Fgr through its SH2 domain requires previous
      autophosphorylation of the kinase and is prevented by subsequent phosphorylation 
      of Tyr-222. Kinetic studies with HS1 and its truncated forms previously
      phosphorylated by Syk and with a peptide substrate reproducing the sequence
      around tyrosine 222 support the view that efficient phosphorylation of HS1 by Src
      family protein kinases entirely relies on TyrP-SH2 domain interaction with
      negligible, if any, contribution of local specificity determinants. Our data
      indicate that the proline-rich region of HS1 bordered by tyrosyl residues
      affected by Syk and Src family kinases represents a functional domain designed to
      undergo a process of sequential phosphorylation.
FAU - Brunati, A M
AU  - Brunati AM
AD  - Dipartimento di Chimica Biologica, Centro di Studio delle Biomembrane del
      Consiglio Nazionale delle Ricerche and Centro Ricerca Interdipartimentale
      Biotecnologie Innovative, University of Padova, 35121 Padova, Italy.
FAU - Donella-Deana, A
AU  - Donella-Deana A
FAU - James, P
AU  - James P
FAU - Quadroni, M
AU  - Quadroni M
FAU - Contri, A
AU  - Contri A
FAU - Marin, O
AU  - Marin O
FAU - Pinna, L A
AU  - Pinna LA
LA  - eng
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 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Blood Proteins)
RN  - 0 (Enzyme Precursors)
RN  - 0 (HCLS1 protein, human)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Proteins)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (SYK protein, human)
RN  - EC 2.7.10.2 (Syk Kinase)
RN  - EC 2.7.10.2 (proto-oncogene proteins c-fgr)
RN  - EC 2.7.10.2 (src-Family Kinases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Amino Acid Sequence
MH  - Blood Proteins/chemistry/*metabolism
MH  - Enzyme Precursors/metabolism
MH  - Intracellular Signaling Peptides and Proteins
MH  - Kinetics
MH  - Molecular Sequence Data
MH  - Molecular Weight
MH  - Peptide Mapping
MH  - Phosphorylation
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Recombinant Proteins/chemistry/metabolism
MH  - Syk Kinase
MH  - src-Family Kinases
EDAT- 1999/03/06 00:00
MHDA- 1999/03/06 00:01
CRDT- 1999/03/06 00:00
PHST- 1999/03/06 00:00 [pubmed]
PHST- 1999/03/06 00:01 [medline]
PHST- 1999/03/06 00:00 [entrez]
AID - 10.1074/jbc.274.11.7557 [doi]
AID - S0021-9258(18)37034-0 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Mar 12;274(11):7557-64. doi: 10.1074/jbc.274.11.7557.