Identification of -R-X-(X)-S/T-X3-S/T- as consensus sequence motif for autophosphorylation-dependent protein kinase

Shiaw Der Yang, Tze Jen Huang, Thomas Soderling

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

To identify consensus sequence motif for a new family of protein kinase termed autophosphorylation-dependent protein serine/threonine kinase (auto- kinase), we have tested several synthetic peptides. The well established protein serine/threonine kinases such as cAMP-dependent protein kinase, Ca2+/calmodulin-dependent protein kinase (CaM-kinase), and protein kinase C were found to be inactive toward phosphorylation of syntide-3 (RPRPASVPPSPSLSRHA), which turned out to be an excellent substrate only for auto-kinase, indicating that syntide-3 is a specific substrate for auto- kinase. Modification of syntide-3 to become RPRPASVPPS/T did not affect the activity of auto-kinase. By contrast, auto-kinase became rather or almost inactive when the peptide was modified to become RPRPASVPPA/G/F/K/R/D/E/Y, indicating that amino acid number 10 in syntide-3 is crucial to the sequence motif recognized by auto-kinase. Phosphorylation of myelin basic protein (MBP) by auto-kinase revealed that auto-kinase predominantly phosphorylates MBP on one particular site with RT-T(p)HYGS as the phosphorylation site sequence, which could not be phosphorylated by any other reported MBP kinases including cAMP-dependent protein kinase, CaM-kinase, protein kinase C, mitogen-activated protein kinase, and kinase FA/GSK-3. Taken together, the results provide initial evidence that -Arg-X-(X)-Ser/Thr-X3-Ser/Thr- may represent a unique consensus sequence motif specifically recognized by autophosphorylation-dependent protein kinase, a new family of multisubstrate/multifunctional protein serine/threonine kinase.

Original languageEnglish (US)
Pages (from-to)29855-29859
Number of pages5
JournalJournal of Biological Chemistry
Volume269
Issue number47
StatePublished - Nov 25 1994
Externally publishedYes

Fingerprint

Consensus Sequence
Protein Kinases
Protein-Serine-Threonine Kinases
Phosphorylation
Myelin Basic Protein
Calcium-Calmodulin-Dependent Protein Kinases
Cyclic AMP-Dependent Protein Kinases
Protein Kinase C
MAP Kinase Kinase Kinases
Glycogen Synthase Kinase 3
Peptides
Mitogen-Activated Protein Kinase Kinases
Substrates
autophosphorylation-dependent multifunctional protein kinase
Amino Acids

ASJC Scopus subject areas

  • Biochemistry

Cite this

Identification of -R-X-(X)-S/T-X3-S/T- as consensus sequence motif for autophosphorylation-dependent protein kinase. / Yang, Shiaw Der; Huang, Tze Jen; Soderling, Thomas.

In: Journal of Biological Chemistry, Vol. 269, No. 47, 25.11.1994, p. 29855-29859.

Research output: Contribution to journalArticle

Yang, Shiaw Der ; Huang, Tze Jen ; Soderling, Thomas. / Identification of -R-X-(X)-S/T-X3-S/T- as consensus sequence motif for autophosphorylation-dependent protein kinase. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 47. pp. 29855-29859.
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