PMID- 10224125
OWN - NLM
STAT- MEDLINE
DCOM- 19990603
LR  - 20211203
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 19
DP  - 1999 May 7
TI  - Thermodynamic and kinetic characterization of the interaction between the Ras
      binding domain of AF6 and members of the Ras subfamily.
PG  - 13556-62
AB  - Cellular signaling downstream of Ras is highly diversified and may involve many
      different effector molecules. A potential candidate is AF6 which was originally
      identified as a fusion to ALL-1 in acute myeloid leukemia. In the present work
      the interaction between Ras and AF6 is characterized and compared with other
      effectors. The binding characteristics are quite similar to Raf and RalGEF, i.e. 
      nucleotide dissociation as well as GTPase-activating protein activity are
      inhibited, whereas the intrinsic GTPase activity of Ras is unperturbed by AF6
      binding. Particularly, the dynamics of interaction are similar to Raf and RalGEF 
      with a lifetime of the Ras. AF6 complex in the millisecond range. As probed by
      31P NMR spectroscopy one of two major conformational states of Ras is stabilized 
      by the interaction with AF6. Looking at the affinities of AF6 to a number of Ras 
      mutants in the effector region, a specificity profile emerges distinct from that 
      of other effector molecules. This finding may be useful in defining the
      biological function of AF6 by selectively switching off other pathways downstream
      of Ras using the appropriate effector mutant. Notably, among the Ras-related
      proteins AF6 binds most tightly to Rap1A which could imply a role of Rap1A in AF6
      regulation.
FAU - Linnemann, T
AU  - Linnemann T
AD  - Abteilung Strukturelle Biologie, Max-Planck-Institut fur Molekulare Physiologie, 
      Postfach 102664, 44026 Dortmund, Germany.
FAU - Geyer, M
AU  - Geyer M
FAU - Jaitner, B K
AU  - Jaitner BK
FAU - Block, C
AU  - Block C
FAU - Kalbitzer, H R
AU  - Kalbitzer HR
FAU - Wittinghofer, A
AU  - Wittinghofer A
FAU - Herrmann, C
AU  - Herrmann C
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 (AFDN protein, human)
RN  - 0 (Phosphorus Isotopes)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - EC 3.6.4.1 (Myosins)
RN  - EC 3.6.4.4 (Kinesins)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - Guanosine Triphosphate/metabolism
MH  - Humans
MH  - Hydrolysis
MH  - Kinesins/*metabolism
MH  - Kinetics
MH  - Molecular Sequence Data
MH  - Myosins/*metabolism
MH  - Phosphorus Isotopes
MH  - Rats
MH  - Sequence Homology, Amino Acid
MH  - Thermodynamics
MH  - ras Proteins/chemistry/*metabolism
EDAT- 1999/05/01 00:00
MHDA- 1999/05/01 00:01
CRDT- 1999/05/01 00:00
PHST- 1999/05/01 00:00 [pubmed]
PHST- 1999/05/01 00:01 [medline]
PHST- 1999/05/01 00:00 [entrez]
AID - 10.1074/jbc.274.19.13556 [doi]
AID - S0021-9258(18)36914-X [pii]
PST - ppublish
SO  - J Biol Chem. 1999 May 7;274(19):13556-62. doi: 10.1074/jbc.274.19.13556.