Structural properties and mechanisms that govern association of C kinase adapter 1 with protein kinase C3 and the cell periphery.

Association of an atypical protein kinase C with an adapter protein can affect the location, activity, substrate specificity, and physiological role of the phosphotransferase. Knowledge of mechanisms that govern formation and intracellular targeting of protein complexes is limited. Caenorhabditis elegans protein kinase C adapter proteins (CKA1 and CKA1S) bind and target and provide prototypes for mechanistic analysis. CKA1 binds an via a phosphotyrosine binding (PTB) domain. A distinct, Arg/Lys-rich N-terminal region targets CKA1 to the cell periphery. We discovered that a short segment ((212)GGIDNGAFHEHEI(224)) of the V(2) (linker) region of creates a binding surface that interacts with the PTB domain of CKA1/CKA1S. The docking domain of duanyu15313 differs from classical PTB ligands by the absence of Tyr and Pro. Substitution of Ile(214), Asn(216), or Phe(219) with Ala abrogates binding of duanyu15313 with CKA1; these residues cooperatively configure a docking site that complements an apolar surface of the CKA1 PTB domain. Phosphorylation site domains (PSD1, residues 11-25; PSD2, residues 61-77) in CKA1 route the adapter (and tethered to the cell periphery. Phosphorylation of Ser(17) and Ser(65) in PSDs 1 and 2 elicits translocation of CKA1 from the cell surface to cytoplasm. Activities of DAG-stimulated and opposing protein Ser/Thr phosphatases can dynamically regulate the distribution of adapter protein between the cell periphery and cytoplasm.

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