Farnesyl pyrophosphate promotes and is essential for the binding of RACK1 with beta-tubulin.
Receptors for activated C kinase (RACKs) are a group of protein kinase C (PKC) binding proteins that have been shown to be crucial in the translocation and subsequent functioning of PKC on activation. RACK1 isolated from BALB/3T3 cells transformed with S-ras(Q61K) exhibits receptor activity for PKCgamma as competent as that of RACK1 from BALB/3T3 cells without transformation. However, the ability of RACK1 from transformed cells to bind with beta-tubulin peptide specific for Taxol (PEPtaxol) is defective. Interestingly, when farnesyl pyrophosphate was added at the submicrogram level, the association between RACK1 and PEPtaxol was enhanced significantly in a dosage-dependent manner. A parallel finding for the enhanced effect of farnesyl pyrophosphate on tubulin binding was established with mice RACK1 expressed in vitro. On the other hand, geranylgeranyl pyrophosphate, and retinoic acid failed to modulate the binding between RACK1 and tubulin. The dissociation of RACK1 and tubulin was not effective at damaging the binding between RACK1 and membrane receptor integrin beta1 in transformed cells. These findings indicate that depletion of farnesyl pyrophosphate provides a mechanism to seal PKC signaling on the membrane with immobile RACK1 and to divert cells to aberrant growth, such as transformation.
Huang
Chein-Fuang
CF
Division of Biochemistry and Molecular Science, Institute of Zoology, Academia Sinica, Nankang 11529, Taipei, Taiwan.
Fan
Jun-Huei
JH
Chuang
Nin-Nin
NN
D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments; D011106:Polyisoprenyl Phosphates / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000302:isolation & purification / Q000378:metabolism*; D012717:Sesquiterpenes; D015398:Signal Transduction / Q000502:physiology*; D014404:Tubulin / Q000378:metabolism*; D015854:Up-Regulation
D010446:Peptide Fragments; D011106:Polyisoprenyl Phosphates; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D012717:Sesquiterpenes; D014404:Tubulin; C004808:farnesyl pyrophosphate; D011493:Protein Kinase C