Rajesh K. Naz

Division of Research, Department of Obstetrics and Gynecology, Medical College of Ohio, Toledo, Ohio, USA

Received 07/23/96; Accepted 07/30/96; On-line 08/15/96

Protein phosphorylation, especially at the tyrosine residues, has been shown to have a definite role in the regulation of function of various receptors (1). It is the most prevalent form of post-translational modification in metazoan cell and along with allosteric modulation, is recognized as a universal mechanism for regulating function of proteins involved in many biological processes. Receptors for several growth factors are themselves tyrosine protein kinases that are activated by ligand binding (1). Protein tyrosine kinases regulate cell proliferation and differentiation, and tyrosine phosphorylation may be the primary, or even the exclusive, indication of signal transduction. Receptor tyrosine kinases participate in transmembrane signaling, whereas the intracellular tyrosine kinases take part in signal transduction within the cell including signal to nucleus (2).

All the receptor tyrosine kinases possess a large glycosylated extracellular ligand binding domain, a single hydrophobic transmembrane region, and a cytoplasmic domain that contains tyrosine kinase catalytic domain (1-3). The tyrosine kinase catalytic domain is the most conserved portion and among other highly conserved sequences of unknown function, it contains a consensus sequence, GlyXGlyXXGlyX Lys, that functions as a part of the binding site for ATP (1, 2). The phosphate group can be incorporated into either the catalytic domain or the regulatory domain(s) of the enzymes. Intra- or intermolecular autophosphorylation of site within the kinase holoenzyme structure is a common, and perhaps a universal theme of these proteins.

Fertilization is a complex process requiring the spermatozoon to undergo a cascade of events before it can fuse with the oocyte plasma membrane (4). Two crucial steps in the fertilization process that sperm undergo are: a) to attain the fertilizing capacity, the physiological process called capacitation, that is followed by acrosomal reaction (exocytosis), and, b) to attach to zona pellucida (ZP) of the ovum, that requires recognition and interaction between complementary molecules present on the spermatozoon and the ZP. The molecules and mechanisms involved in capacitation/acrosomal exocytosis, and ZP binding are not clearly understood (4). It needs to be elucidated whether there is a signal transduction pathway(s) involved in these crucial steps. The aims of this review article are: 1) to review the sperm surface molecules that are involved in these two processes namely capacitation/acrosomal exocytosis and ZP binding, and, 2) to examine evidence whether or not there is membrane tyrosine phosphorylation leading to signal transduction in the crucial steps of fertilization.