Tyrosine-phosphorylated calmodulin has reduced biological activity.

Abstract:

:Calmodulin is phosphorylated by the purified insulin receptor on tyrosine residues with a maximum stoichiometry of 1 mol phosphate/mol of calmodulin. Isolated tryptic phosphopeptides were sequenced by manual Edman degradation and demonstrated that calmodulin is equally phosphorylated on tyrosine 99 and tyrosine 138. Phosphorylated calmodulin has a decreased affinity (K0.5 = 4.2 nM) for the 63-kDa isozyme of cyclic nucleotide phosphodiesterase compared to nonphosphorylated calmodulin (K0.5 = 2.1 nM). The K0.5 for Ca2+ is marginally increased from 2.8 to 3.2 microM in the presence of phosphotyrosyl calmodulin. The effect of the calmodulin antagonist, mastoparan, was investigated to determine whether mastoparan would differentially inhibit calmodulin- or phosphocalmodulin-dependent enzyme activity. The IC50 of mastoparan is fourfold lower for phosphotyrosyl calmodulin compared to nonphosphorylated calmodulin. Phosphorylation of calmodulin may provide a mechanism for the differential regulation of calmodulin-dependent enzymes. These observations further support a potentially important regulatory function of calmodulin phosphorylation in signal transduction.

journal_name

Arch Biochem Biophys

authors

Williams JP,Jo H,Sacks DB,Crimmins DL,Thoma RS,Hunnicutt RE,Radding W,Sharma RK,McDonald JM

doi

10.1006/abbi.1994.1479

subject

Has Abstract

pub_date

1994-11-15 00:00:00

pages

119-26

issue

1

eissn

0003-9861

issn

1096-0384

pii

S0003986184714792

journal_volume

315

pub_type

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