PMID- 10085136
OWN - NLM
STAT- MEDLINE
DCOM- 19990429
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 13
DP  - 1999 Mar 26
TI  - Interactions between two cytoskeleton-associated tyrosine kinases:
      calcium-dependent tyrosine kinase and focal adhesion tyrosine kinase.
PG  - 8917-24
AB  - The calcium-dependent tyrosine kinase (CADTK), also known as
      Pyk2/RAFTK/CAKbeta/FAK2, is a cytoskeleton-associated tyrosine kinase. We
      compared CADTK regulation with that of the highly homologous focal adhesion
      tyrosine kinase (FAK). First, we generated site-specific CADTK mutants. Mutation 
      of Tyr402 eliminated autophosphorylation and significantly decreased kinase
      activity. Mutation of Tyr881, a putative Src kinase phosphorylation site
      predicted to bind Grb2, had little effect on CADTK regulation. Src family
      tyrosine kinases resulted in CADTK tyrosine phosphorylation even when
      co-expressed with the Tyr402/Tyr881 double mutant, suggesting that Src/Fyn etc.
      phosphorylate additional tyrosine residues. Interestingly, CADTK
      tyrosine-phosphorylated FAK when both were transiently expressed, but FAK did not
      phosphorylate CADTK. Biochemical experiments confirmed direct CADTK
      phosphorylation of FAK. This phosphorylation utilized tyrosine residues other
      than Tyr397, Tyr925, or Tyr576/Tyr577, suggesting that new SH2-binding sites
      might be created by CADTK-dependent FAK phosphorylation. Last, expression of the 
      CADTK carboxyl terminus (CRNK) abolished CADTK but not FAK autophosphorylation.
      In contrast, FAK carboxyl terminus overexpression inhibited both FAK and CADTK
      autophosphorylation, suggesting that a FAK-dependent cytoskeletal function may be
      necessary for CADTK activation. Thus, CADTK and FAK, which both bind to some, but
      not necessarily the same, cytoskeletal elements, may be involved in coordinate
      regulation of cytoskeletal structure and signaling.
FAU - Li, X
AU  - Li X
AD  - Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel
      Hill, Chapel Hill, North Carolina 27599-7295, USA.
FAU - Dy, R C
AU  - Dy RC
FAU - Cance, W G
AU  - Cance WG
FAU - Graves, L M
AU  - Graves LM
FAU - Earp, H S
AU  - Earp HS
LA  - eng
GR  - CA65910/CA/NCI NIH HHS/United States
GR  - GM54010/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (pervanadate)
RN  - 3WHH0066W5 (Vanadates)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 1)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 2)
RN  - EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (PTK2 protein, human)
RN  - EC 2.7.10.2 (Ptk2 protein, rat)
RN  - EC 2.7.10.2 (Ptk2b protein, rat)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Binding Sites/genetics
MH  - Calcium/*pharmacology
MH  - Cell Adhesion Molecules/*metabolism
MH  - Cell Line
MH  - Cytoskeleton/*enzymology
MH  - Enzyme Activation/drug effects
MH  - Focal Adhesion Kinase 1
MH  - Focal Adhesion Kinase 2
MH  - Focal Adhesion Protein-Tyrosine Kinases
MH  - Gene Expression Regulation, Enzymologic/genetics
MH  - Humans
MH  - Mutagenesis, Site-Directed
MH  - Mutation/genetics
MH  - Phosphorylation
MH  - Protein-Tyrosine Kinases/genetics/*metabolism
MH  - Rats
MH  - Vanadates/pharmacology
MH  - src Homology Domains/genetics
MH  - src-Family Kinases/metabolism
EDAT- 1999/03/20 00:00
MHDA- 1999/03/20 00:01
CRDT- 1999/03/20 00:00
PHST- 1999/03/20 00:00 [pubmed]
PHST- 1999/03/20 00:01 [medline]
PHST- 1999/03/20 00:00 [entrez]
AID - 10.1074/jbc.274.13.8917 [doi]
AID - S0021-9258(19)87413-6 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Mar 26;274(13):8917-24. doi: 10.1074/jbc.274.13.8917.