Post-proliferative cyclin E-associated kinase activity in differentiated osteoblasts: inhibition by proliferating osteoblasts and osteosarcoma cells

UMMS Affiliation

Department of Cell Biology

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Document Type



Animals; CDC2 Protein Kinase; *CDC2-CDC28 Kinases; Cell Differentiation; Cell Division; Cyclin-Dependent Kinase 2; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinases; effects; Cyclins; Hot Temperature; Osteoblasts; Osteosarcoma; Phosphorylation; Protein-Serine-Threonine Kinases; Rats; Retinoblastoma Protein; Tumor Cells, Cultured


Cell Biology


Spontaneous differentiation of normal diploid osteoblasts in culture is accompanied by increased cyclin E associated kinase activity on (1) the retinoblastoma susceptibility protein pRB, (2) the p107 RB related protein, and (3) two endogenous cyclin E-associated substrates of 78 and 105 kD. Activity of the differentiation-related cyclin E complexes (diff.ECx) is not recovered in cdc2 or cdk2 immunoprecipitates. Phosphorylation of both the 105 kD endogenous substrate and the p107 exogenous substrate is sensitive to inhibitory activity (diff.ECx-i) present in proliferating osteoblasts. This inhibitory activity is readily recruited by the cyclin E complexes of differentiated osteoblasts but is not found in cyclin E immunoprecipitates of the proliferating cells themselves. Strong inhibitory activity on diff.ECx kinase activity is excerted by proliferating ROS 17/2.8 osteosarcoma cells. However, unlike the normal diploid cells, the diff.ECx-i activity of proliferating ROS 17/2.8 cells is recovered by cyclin E immunoprecipitation. The cyclin-dependent kinase inhibitor p21CIP1/WAF1 inhibits diff.ECx kinase activity. Thus, our results suggest the existence of a unique regulatory system, possibly involving p21CIP1/WAF1, in which inhibitory activity residing in proliferating cells is preferentially targeted towards differentiation-related cyclin E-associated kinase activity.


J Cell Biochem. 1997 Aug 1;66(2):141-52.

Journal/Book/Conference Title

Journal of cellular biochemistry

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