The noncatalytic domains of Lck regulate its dephosphorylation by CD45.
The Src-family tyrosine kinase, Lck, contains two key regulatory phosphotyrosine residues, tyrosine 394 (Tyr-394) and tyrosine 505 (Tyr-505), both of which can be dephosphorylated by CD45. Here, the interaction of CD45 with its substrate, Lck, was determined to be complex, involving multiple interactions with both the catalytic and noncatalytic regions of Lck. CD45 preferentially dephosphorylated Tyr-394 over Tyr-505 in Lck. This was not due to sequence specificity surrounding the phosphotyrosine, but was due to the noncatalytic domains of Lck. The interactions with the noncatalytic domains of Lck and CD45 enhanced the dephosphorylation of Tyr-394 whereas intramolecular interactions within Lck reduced, but did not abolish, the dephosphorylation of Tyr-505. This demonstrates that the noncatalytic domains of Lck regulate the dephosphorylation of both Tyr-394 and Tyr-505 by CD45.
Lefebvre
Dennis C
DC
Department of Microbiology and Immunology, University of British Columbia, #300-6174 University Boulevard, Vancouver, BC, Canada V6T 1Z3.
Felberg
Jackie
J
Cross
Jennifer L
JL
Johnson
Pauline
P
D000494:Allosteric Regulation / Q000502:physiology; D000495:Allosteric Site / Q000502:physiology; D000818:Animals; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism*; D051379:Mice; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D017493:Leukocyte Common Antigens