Cyclins, cyclin-dependent kinases (Cdks), and cyclin-dependent kinase inhibitors (CdkIs) are essential for cell-cycle control in eukarytotes. Cyclins, regulatory subunits, bind to cyclin-dependent kinases (Cdks), catalytic subunits, to form active cyclin-Cdk complexes. Cdk subunits by themselves are inactive and binding to a cyclin is required for their activity. Cyclins A, B1, D and E undergo periodic synthesis and degradation, thereby providing a mechanism to regulate Cdk activity throughout the cell cycle. Additionally, Cdk activity is further regulated by activating and inhibitory phosphorylations, and small proteins (p15, p16, p18, p19, p21 and p27), called inhibitors of Cdk activity, that bind to cyclins, Cdks, or cyclin- Cdk complexes. Cdk4 was originally called PSK-J3, and following demonstration of its association with D-type cyclins, became known as Cdk4. D-type cyclins also associate with Cdks 2 and 5, although Cdk4 appears to be the most abundant partner. The D-type cyclins (D1, D2, and D3) are expressed in response to growth factors or mitogens, and rapidly degrade when mitogens are withdrawn. D cyclins appear to promote G0 to G1 transitions and the rate of G1 progression. For example, cyclin D-Cdk4 and cyclin D-Cdk6 complexes phosphorylate the retinoblastoma protein (Rb) which removes the G1 phase block caused by underphosphorylated Rb. Cdk4 has a molecular weight of ~32 kD. Clone DCS-156 recognizes human and mouse Cdk4. A recombinant protein fragment from the C-terminal end of human Cdk4 was used as immunogen.
