TLS Online TPP Program

#Id: 8611

#Section 3: Genetics, Cellular and Molecular Biology

Nonphosphorylated CDK bound to one of its cyclin partners has minimal but detectable protein kinase activity in vitro, although it may be essentially inactive in vivo.

TLS Online TPP Program

#Id: 8612

#Section 3: Genetics, Cellular and Molecular Biology

Phosphorylation of a critical threonine residue in the activation loop, Thr-160, allowing substrates to access the active site of the CDK

TLS Online TPP Program

#Id: 8613

#Section 3: Genetics, Cellular and Molecular Biology

Threonine -160 phosphorylation is mediated by 

CDK-activating kinase (CAK)

TLS Online TPP Program

#Id: 8614

#Section 3: Genetics, Cellular and Molecular Biology

Two inhibitory phosphorylations on CDK play a critical role in controlling CDK activity:

Y15

T14

TLS Online TPP Program

#Id: 8615

#Section 3: Genetics, Cellular and Molecular Biology

Y15 & T14 are situated in the G-loop of the CDK, containing the consensus sequence GEGT14Y15GVV

TLS Online TPP Program

#Id: 8616

#Section 3: Genetics, Cellular and Molecular Biology

Phosphorylation of T14 and Y15 in this G-loop

introduces negative charge that electrostatically interferes with the binding of ATP in the catalytic pocket.