Structural Properties and Mechanisms that Govern Association of C Kinase Adapter 1 with Protein Kinase C3 and the Cell Periphery

Lihua Zhang, Shi Lan Wu, Charles S. Rubin

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Association of an atypical protein kinase C (aPKC) 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 aPKC·adapter protein complexes is limited. Caenorhabditis elegans protein kinase C adapter proteins (CKA1 and CKAIS) bind and target aPKCs and provide prototypes for mechanistic analysis. CKA1 binds an aPKC (PKC3) 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 (212GGIDNGAFHEHEI224) of the V 2 (linker) region of PKC3 creates a binding surface that interacts with the PTB domain of CKA1/CKA1S. The docking domain of PKC3 differs from classical PTB ligands by the absence of Tyr and Pro. Substitution of Ile 214, Asn216, or Phe219 with Ala abrogates binding of PKC3 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 PKC3) to the cell periphery. Phosphorylation of Ser 17 and Ser65 in PSDs 1 and 2 elicits translocation of CKA1 from the cell surface to cytoplasm. Activities of DAG-stimulated PKCs and opposing protein Ser/Thr phosphatases can dynamically regulate the distribution of adapter protein between the cell periphery and cytoplasm.

Original languageEnglish (US)
Pages (from-to)10476-10484
Number of pages9
JournalJournal of Biological Chemistry
Volume276
Issue number13
DOIs
StatePublished - Mar 30 2001

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Phosphotyrosine
Protein Kinases
Structural properties
Phosphotransferases
Phosphorylation
Cytoplasm
Proteins
Caenorhabditis elegans Proteins
Protein Transport
Substrate Specificity
Phosphoric Monoester Hydrolases
Protein Kinase C
Ligands
Substitution reactions
Substrates
PKC-3 protein

ASJC Scopus subject areas

  • Biochemistry

Cite this

Structural Properties and Mechanisms that Govern Association of C Kinase Adapter 1 with Protein Kinase C3 and the Cell Periphery. / Zhang, Lihua; Wu, Shi Lan; Rubin, Charles S.

In: Journal of Biological Chemistry, Vol. 276, No. 13, 30.03.2001, p. 10476-10484.

Research output: Contribution to journalArticle

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