| Regulatory protein/complex | Mechanism of regulation | Specific modification site(s) / interaction details | Functional outcome for CDK16 | Tissue / cellular context observed |
|---|---|---|---|---|
| Cyclin Y (CCNY) | Direct binding; regulatory subunit association | CCNY binds CDK16, with binding reported at the plasma membrane and requiring a region upstream of the kinase domain; CCNY-dependent activation is a defining feature of CDK16/PCTAIRE signaling (pqac-00000000, pqac-00000014) | Promotes CDK16 kinase activity and helps localize/organize CDK16 signaling at membranes; supports roles in neurite/presynaptic trafficking, mitotic regulation, and other differentiated-cell functions (pqac-00000000, pqac-00000014) | Observed in overexpression systems and endogenous mammalian contexts; emphasized in brain/testis-associated biology and plasma membrane signaling (pqac-00000000, pqac-00000014) |
| Cyclin Y-like 1 (CCNYL1) | Direct binding; regulatory subunit association | CDK16 interacts with CCNYL1; complex formation has been specifically linked to spermatogenesis, though precise CDK16 phosphosite control by CCNYL1 was not established in the available context (pqac-00000006, pqac-00000014) | Supports CDK16 function in male germ-cell differentiation and sperm development; likely contributes to CDK16 stability and/or activation in testis (pqac-00000006, pqac-00000014) | Testis, especially spermatogenesis / elongated spermatids / sperm maturation contexts (pqac-00000006, pqac-00000014) |
| PKA | Phosphorylation of CDK16 | PKA phosphorylates CDK16 on four serine residues; Ser153 is highlighted as the main site. Phosphorylation of Ser153 inhibits CCNY binding, making cyclin association phosphorylation-dependent (pqac-00000006, pqac-00000014) | Regulates CDK16 activation state by modulating cyclin binding; Ser153 phosphorylation inhibits CCNY association and thereby alters kinase activation/localization behavior (pqac-00000006, pqac-00000014) | Demonstrated in mechanistic studies of CDK16 regulation; discussed in mammalian cellular systems and testis/brain-related CDK16 biology (pqac-00000006, pqac-00000014) |
| CDK5/p35 complex | Phosphorylation of CDK16 | CDK5/p35 phosphorylates CDK16 at Ser95 (pqac-00000014) | Increases CDK16 kinase activity (pqac-00000014) | Brain / neuronal context, where both CDK5 signaling and PCTAIRE kinases are prominently studied (pqac-00000014) |
| 14-3-3 proteins | Protein interaction; binding to phosphorylated CDK16-associated states | 14-3-3 proteins are reported CDK16 interactors; their binding may depend on prior phosphorylation and may increase basal CDK16 kinase activity, although the exact interaction architecture remains unresolved (pqac-00000003, pqac-00000014) | Potentially enhances basal kinase activity and contributes to non-canonical activation/regulatory complex formation (pqac-00000003, pqac-00000014) | Reported in brain and broader mammalian cell studies; discussed especially in relation to unclear endogenous activation mechanisms (pqac-00000003, pqac-00000014) |
| AMPK | Indirect activation via phosphorylation of CCNY | AMPK phosphorylates CCNY at Ser326, which promotes CCNY-CDK16 interaction and increases CDK16 kinase activity; the CCNY/CDK16 complex is described as an AMPK substrate/effector in autophagy regulation (pqac-00000006, pqac-00000007) | Enhances CCNY-CDK16 complex formation and activates CDK16 in nutrient/energy-stress signaling; promotes autophagy-related CDK16 function (pqac-00000006, pqac-00000007) | Autophagy-related cellular contexts, including studies linking AMPK, CCNY/CDK16, ULK1/Beclin1-dependent macroautophagy, and vesicle/actin-associated regulation (pqac-00000006, pqac-00000007) |


*Table: This table summarizes the main reported regulators of CDK16 activation and signaling, including binding partners and upstream kinases. It is useful for distinguishing direct activators from phosphorylation-based modulators and for tracking the tissue contexts in which each mechanism has been observed.*