TY  - JOUR
AU  - Hofmann, G.
AU  - Schweimer, K.
AU  - Kiessling, A.
AU  - Hofinger, E.
AU  - Bauer, F.
AU  - Hoffmann, S.
AU  - Rosch, P.
AU  - Campbell, I. D.
AU  - Werner, J. M.
AU  - Sticht, H.
TI  - Binding, domain orientation, and dynamics of the Lck SH3-SH2 domain pair and comparison with other Src-family kinases
JO  - Biochemistry
VL  - 44
SN  - 0006-2960
CY  - Columbus, Ohio
PB  - American Chemical Society
M1  - PreJuSER-49408
SP  - 13043 - 13050
PY  - 2005
N1  - Record converted from VDB: 12.11.2012
AB  - The catalytic activity of Src-family kinases is regulated by association with its SH3 and SH2 domains. Activation requires displacement of intermolecular contacts by SH3/SH2 binding ligands resulting in dissociation of the SH3 and SH2 domains from the kinase domain. To understand the contribution of the SH3-SH2 domain pair to this regulatory process, the binding of peptides derived from physiologically relevant SH2 and SH3 interaction partners was studied for Lck and its relative Fyn by NMR spectroscopy. In contrast to Fyn, activating ligands do not induce communication between SH2 and SH3 domains in Lck. This can be attributed to the particular properties of the Lck SH3-SH2 linker which is shown to be extremely flexible thus effectively decoupling the behavior of the SH3 and SH2 domains. Measurements on the SH32 tandem from Lck further revealed a relative domain orientation that is distinctly different from that found in the Lck SH32 crystal structure and in other Src kinases. These data suggest that flexibility between SH2 and SH3 domains contributes to the adaptation of Src-family kinases to specific environments and distinct functions.
KW  - Humans
KW  - Ligands
KW  - Lymphocyte Specific Protein Tyrosine Kinase p56(lck): chemistry
KW  - Lymphocyte Specific Protein Tyrosine Kinase p56(lck): metabolism
KW  - Nuclear Magnetic Resonance, Biomolecular
KW  - Peptides: metabolism
KW  - Protein Binding
KW  - Protein Structure, Tertiary
KW  - Proto-Oncogene Proteins c-fyn: chemistry
KW  - src Homology Domains
KW  - src-Family Kinases: chemistry
KW  - Ligands (NLM Chemicals)
KW  - Peptides (NLM Chemicals)
KW  - FYN protein, human (NLM Chemicals)
KW  - Lymphocyte Specific Protein Tyrosine Kinase p56(lck) (NLM Chemicals)
KW  - Proto-Oncogene Proteins c-fyn (NLM Chemicals)
KW  - src-Family Kinases (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:16185072
UR  - <Go to ISI:>//WOS:000232253700013
DO  - DOI:10.1021/bi050814y
UR  - https://juser.fz-juelich.de/record/49408
ER  -