Kinases and Phosphatases

Protein kinases phosphorylate other proteins. Some are stimulated at the beginning of signal transduction pathways by specific growth factors, whereas others are stimulated at later points during the signal pathway by the binding of second messengers or by phosphorylation. Some kinases are membrane-bound, but the majority are free in the cytoplasm. Most protein kinases are multimeric, consisting of separate catalytic and regulatory subunits.

Protein kinases are categorized on the basis of which amino acids they phosphorylate (e.g., tyrosine and serine-threonine) as well as on the basis of their activity (e.g., cAMP-dependent, cyclin-dependent, etc.). Membrane tyrosine kinases and serine-threonine kinases are generally stimulated directly by a chemical signal. Protein kinase α(PKA) and protein kinase G (PKG) are soluble serine-threonine kinases activated by cAMPand cGMP, respectively. PKC is used to label a large family of serine- threonine protein kinases that are stimulated directly by the second messengers DG and/or Ca²⁺. A protein kinase that requires the calcium ion binding protein calmodulin and Ca²⁺ for its activity is known as calmodulin-calcium-dependent protein kinase. Ca²⁺ pores in the plasma membrane and in the endoplasmic reticulum are opened by the binding of IP₃ to the pores. A protein kinase that is required for progression through the cell cycle is dependent upon a number of protein stimulators called cyclins.

Because protein kinases are part of most signal pathways, they control almost every aspect of cellular physiology. Thus, control of a cell's physiology is affected by the phosphorylated state of its proteins. If phosphorylation affects a response, then there must be enzymes that reverse that response. Protein phosphatases remove phosphate groups from proteins. Some phosphatases are activated by phosphorylation, some by a calmodulin-Ca²⁺ complex, and some by inhibitory proteins.